Glossary SAS actives August 2013 By Hannah Sivak, PhD Biochemist, Skin Actives Scientific LLC Gilbert, Arizona,

USA Notes: if you don't find the term you are looking for in alphabetical order, please do a search using "find" in this document (examples: gamma oryzanol is listed as oryzanol (gamma) and genistein is within the Elixir 10 entry). For non active ingredients (formulation basics) please see the Basics document (coming soon). ABCDEFGHIJKLMNOPQRSTUZ A Aai palm (Euterpe oleracea) fruit extract http://www.skinactives.com/Acai-Extract.html Aai extract contains anthocyanins (cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside) and phenolics. The fruit pulp is rich in polyphenols with high antioxidant activity, scavenges peroxyl radicals and reduces proliferation of cancer cells. Anthocyanins are responsible for the deep purple color of thios extract.
Del Pozo-Insfran, David; Percival, Susan S.; Talcott, Stephen T. (2006) Aai (Euterpe oleracea Mart.) Polyphenolics in Their Glycoside and Aglycone Forms Induce Apoptosis of HL-60 Leukemia Cells. J. Agricultural and Food Chemistry, 54:1222-1229. Lichtenthaeler, Ramona; Rodrigues, Roberta Belandrino; Maia, Jose Guilherme S.; Papagiannopoulos, Menelaos; Fabricius, Heinz; Marx, Friedhelm Total oxidant scavenging capacities of Euterpe oleracea Mart. (Acai) fruits (2005) Intl. Journal of Food Sciences and Nutrition, 56:53-64. Gallori, S.; Bilia, A. R.; Bergonzi, M. C.; Barbosa, W. L. R.; Vincieri, F. F. (2004) Polyphenolic constituents of fruit pulp of Euterpe oleracea Mart. (Aai palm). Chromatographia 59: 739-743.

Figure. Euterpe olearacea (Aai)

Adenosine triphosphate http://www.skinactives.com/ATP-Adenosine-triphosphate.html There is no such thing as "most important molecule in life" (because life requires an enormous number of molecules to support its complexity), but if pressed I would choose ATP for the title. This is life's energy currency, the universal energy storage unit, used in practically every synthetic reaction that happens not just in our bodies but in all animals, plants and bacteria (and even in viruses when they are directing traffic in the host). I am including ATP in our line of actives NOT because it will solve all your problems, it will not. First of all, ATP is being formed and broken continuously, so any energy stored in the gram of ATP we sell you will be used up almost instantly. But the ADP and phosphate formed as a result will be used and reused by your body, so there is no waste here.

Figure: Adenine triphosphate

Alpha hydroxy acids (used for exfoliation) Including: lactic, mandelic, malic, citric, glycolic, etc. In the figure, the "alpha" indicates the alpha Carbon (relative to the carboxylic acid), to which the hydroxy group is attached.

Alpha hydroxyl acids are weak acids (weakly ionized) used as exfoliants because they are safe to use at relatively high concentrations. Although present in fruits and milk, these days the acids are likely to be obtained by bacterial fermentation. As far as exfoliation power and relative safety are concerned, the concentration of the acid is not as important as the final pH (determined by the molar concentration and the tendency of the acid to dissociate, measured by the pK). Many products touting high concentrations of the acid have been buffered (pH has been raised) using a base, so that most of the acid is present as a salt and the exfoliation power will be greatly diminished. Note: By decreasing skin thickness, exfoliation increases sensitivity to UV. SAS sells an alpha/beta exfoliant, see http://www.skinactives.com/Alpha-Beta-Exfoliator.html Allantoin http://www.skinactives.com/Allantoin.html Allantoin [(2,5-Dioxo-4-imidazolidinyl) urea] is classified by the FDA as an Over-The-Counter (OTC) Category I (safe and effective) active ingredient skin protectant. It is FDA approved for this use at 0.5% to 2.0% in formulations (you will not get much more than this to dissolve in water anyway). If you include it in your formulations and on your ingredient labels, but make no drug claims for it, it remains a cosmetic ingredient.

Figure. Allantoin Aloe vera http://www.skinactives.com/Aloe-Extract.html Obtained from the Aloe barbadensis plant, this gel improves skin hydration, has antiinflammatory activity and helps healing of cuts, grazes, burns and insect bites. It prevents immune suppression caused by UVB by repairing damage to epidermal Langerhans cells. Aloe vera contains a pharmacologically active chemical, emodin, responsible for the gel antitumor activity. Special polysaccharides, including acetylated mannans, contribute the immunostimulant properties of Aloe vera. Also present in the gel are salicylate and a carboxypeptidase, responsible in part for the anti-inflammatory activity of Aloe vera gel. Alpha lipoic acid http://www.skinactives.com/Alpha-Lipoic-Acid-ALA.html
Other names: R--Lipoic acid (alpha lipoic acid); Thioctic acid; 6,8-Dithiooctanoic acid

Alpha lipoic acid (ALA) is good and essential for cell function, but not essential in the nutritional sense because our bodies make it. Older skin may be "starved" of this very important antioxidant and cofactor. Lipoic acid, a naturally occurring dithiol complex, is the prosthetic (i.e. non-proteic) group of several enzymes, including the transacetylase part of the enzyme complex that catalyzes the decarboxylation of pyruvate so that the remaining 2-carbon group can enter the Krebs cycle. Aside from its fundamental role in enzyme function, in vitro and in vivo studies suggest that ALA also acts as a powerful micronutrient with diverse pharmacological and antioxidant properties. ALA is quickly trapped ("sequestered") by cellular membranes, so it does not get far. So if you want to protect yourself more effectively, try our lipophilic antioxidant mix containing lipoic acid, astaxanthin, vitamin E, tocotrienol and tetrahydrocurcuminoids.

Amino acids (SAS Amino booster) http://www.skinactives.com/Amino-Booster.html

An SAS proprietary complex containing the 20 amino acids found in proteins to ensure optimal nutrition of keratinocytes, this mix provides all amino acids optimal concentrations, which is different for each amino acid. Contains all the essential and non-essential amino acids that aging skin needs. L-Glutamine, L-Arginine, L-Leucine, L-Serine, L-Cysteine, L-Valine, L-Proline, L-Lysine, Glycine, LAsparagine, L-Glutamic Acid, L-Threonine, L-Alanine, L-Phenylalanine, L-Methionine, L-Aspartic Acid, L-Tyrosine, L-Tryptophan, L-Histidine, L-Isoleucine In bold: essential amino acids Note: It is interesting that there is a whole skin care line (AminoGenesis) based on the use of amino acids, but even this line does not get their amino acids right. For example, they seem to have forgotten tryptophan, an essential amino acid, at least in their ingredient list. Other lines use hydroxyproline, a modified amino acid that cant be used in the synthesis of protein, but why let biochemistry interfere with marketing? NOTE: Please keep refrigerated until use. A cream or serum made with this booster will also benefit from refrigeration.

Figure. Amino acids molecular weights and structures, and one and 3-letter abbreviations. Aminobutyric acid (gamma) http://www.skinactives.com/Aminobutyric-Acid-GABA.html

GABA is a non-essential amino acid necessary for brain metabolism. GABA is used in skin care to lessen the effects of wrinkles as part of an anti-aging regimen. GABA assists Niacinamide and Inositol in preventing anxiety and works in the body much like a natural tranquilizer. According

to recent research "the gamma-aminobutyric acid (A)-like receptor associated with skin barrier homeostasis and regulation of the receptor (could be) clinically effective for barrier dysfunctional or epidermal hyperproliferative diseases." Amla (Emblica officinalis) fruit extract http://www.skinactives.com/Amla-Extract-Phyllantus-emblica.html With iron and copper chelating ability, this extract is a perfect complement for chrysin in the treatment of dark under-eye circles. Amla helps protect the skin from the damaging effects of free radicals, and metal-induced oxidative stress. Contains polyphenols (tannins) like gallic acid and ellagic acid, linked together to make other tannins. Amla extract has been found to have chemopreventive acitivity, i.e. the capacity to prevent cancer brought about by chemical cancer causing agents.
Sancheti Garima; Jindal Archana; Kumari Rimpu; Goyal P K (2005) Chemopreventive action of Emblica officinalis on skin carcinogenesis in mice. Asian Pacific J. cancer prevention. 6: 197-201. Anilakumar, K. R.; Nagaraj, N. S.; Santhanam, K. (2004) Protective effects of amla on oxidative stress and toxicity in rats challenged with dimethyl hydrazine. Nutrition Research 24: 313-319. Sumitra, Miriyala, Manikandan, Panchatcharam, Gayathri, Vinaya Subramani, (Mahendran, Panchatcharam, Suguna, Lonchin (2009) Emblica officinalis exerts wound healing action through upregulation of collagen and extracellular signal-regulated kinases (ERK1/2). Wound Repair and Regeneration, 17: 99-107.

Figure. Amla. From Herbarium Blackwellianum emendatum et auctum, idest, Collectio stirpium : Quae in pharmacopoliis ad medicum asservantur, quarum descriptio et vires ... / Elisabethae Blackwell ; cum praefatione Christoph. Iacobi Trew ; excudit figuras pinxit atque in aes incidit Nicolaus Fridericus Eisenbergerus / Vol. II Edition : Nuremberg : Christian de Launoy, 1760

Figure. Amla, from a series of Indian stamps on medicinal plants.

Andrographis paniculata extract http://www.skinactives.com/Andrographis-paniculata.html A bitter Indian herb used in Ayurveda medicine as Kalmegh or Kalamegha, and known by common names like Maha-tita. Skin inflammation is a persistent problem for so many people and OTC creams containing cortisone can only be used short term (cortisone will thin the skin and should not be used on a long term basis). So it is really nice when scientific research comes up with an active with anti-inflammatory properties and no apparent side effects. You will find Andrographis in our anti-inflammatory cream, or you can mix your own in any cream and lotion you like (make sure it dissolves well first). The mechanism of activity of andrographolide is through the inhibition of nuclear factor-kappa, a central transcriptional factor and a regulator of many genes involved in immunological responses.

Figure. Andrographolide, one of the active chemicals responsible for the activity of Andrographis paniculata extract.

Antioxidant booster http://www.skinactives.com/Antioxidant-Booster.html Please see also individual components, i.e. Pomegranate (Punica Granatum) Seed Oil, Tocotrienols, Alpha-D-Tocopherol (Vitamin E), Astaxanthin, Lycopene, Lutein, Alpha Lipoic Acid, Beta Carotene. The antioxidant booster is a proprietary mix containing a synergistic mixture of antioxidants that will protect skin lipids and cell membranes. This is our best and simplest antioxidant mix, easy to use and perfect for use with all our bases. Apigenin A phenolic flavonoid found in chamomile and many other plants, this antioxidant has antiinflammatory, chemopreventive activity against skin cancer and prevents UVA and B induced skin cancer. It may also help prevent skin aging by UV through inhibition of metalloproteinases and antioxidant activity.

Figure: Apigenin.

Apple pectin is a complex polysaccharide that contains rhamnose, a methylated pentose sugar. Apparently, fibroblasts contain receptors for rhamnose, and when rhamnose binds to these receptors it results in increased synthesis of collagen and strengthened epidermal-dermal junction. Apple pectin may help thicken skin thinned by aging. Arbutin http://www.skinactives.com/Arbutin-alpha.html Arbutin (a.k.a. beta arbutin, ursine) is a glycosilated hydroquinone present in the leaves of the bearberry (Arctostaphylos uva-ursi) and responsible for the skin lightening properties of the plant extract. Just like hydroquinone, the shape of arbutin resembles the amino acid tyrosine enough to fool tyrosinase, the enzyme that catalyzes the first transformation of tyrosine into melanin. Inhibition of the enzyme in this way is called competitive because the false substrate, arbutin, competes with the real one, tyrosine, for the active site of the enzyme. Other properties: arbutin is also an antioxidant, alleviating oxidative stress responses such as leukocyte infiltration and hydrogen peroxide generation by chemical agents. Notes: Shiseido Whitess contains arbutin. There is also a synthetic arbutin with the glycosidic link in alpha, there is no much information on it and we dont use it or sell it.

Figure: arbutin (beta) Argan oil The Argan tree, Argania spinosa, is endemic to Morocco, and it provides food, shelter and its deep roots help prevent soil erosion and desertification; its shade allows for the cultivation of other agricultural products and its leaves and fruit provide food for animals. Cultivation of argan tree helps shading pasture grasses and helps to replenish aquifers.

As for fatty acid composition, argan oil will supply essential fatty acids to the skin. It contains about 43% oleic acid, 37% linolenic, with the rest being palmitic, stearic (and a hint of linolenic) acids. Then there are the extras: sterols, tocopherols, carotenes. And some phenols like oleuropein and catecols. These extras include phospholipids and help prevent oxidation (rancidity) of this oil. An extra bonus: much of the argan oil produced today is made by a number of women's co-operatives.

Figure: Argan oil is pressed from the kernels of the Argan tree fruit.

Arthrospira extract - This extract provides proteins, carbohydrates, essential fatty acids, vitamins, minerals, carotenoids, and even some sulfolipids that seem to have antiviral properties. The anti-inflammatory and anti-allergic properties of this extracts make it an essential active for eczema, psoriasis and other skin affections. We do not sell this extract separately but it is present in our Ultramarine sea kelp bioferment (http://www.skinactives.com/Sea-Kelp-Ultramarine.html)
Naunyn-Schmiedebergs (2000) Inhibition of croton oil-induced oedema in mice ear skin by capsular polysaccharides from Cyanobacteria. Archines of Pharmacology, 361: 460-464 Kim, HM, Lee, EH, Cho, MM, Moon, YH. (1998) Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by Spirulina. Pharmacology, 55: 1071-1076. Yang, HN, Lee, EH and Kim, HM (1997) Spirulina platensis inhibits anaphylactic reaction. Life Sciences, 61: 1237-1244. Remirez, D., Ledon, N., Gonzalez, R. (2002) Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response. Inflammation, 11: 81-85.

Ascorbic acid (L-) http://www.skinactives.com/Ascorbic-Acid--L-Vitamin-C.html This is vitamin C, a water-soluble antioxidant. It is also a cofactor for an enzyme crucial in the synthesis of collagen, prolyl hydrolase.

As an antioxidant agent, vitamin C scavenges and destroys reactive oxidizing agents and other free radicals. Because of this ability, it provides an important protection against damage induced by UV radiation (and the DNA mutations and cancer that may result from it). Vitamin C also improves skin elasticity, decreases wrinkles by stimulating collagen synthesis, reduces erythema, promotes wound healing and suppresses cutaneous pigmentation. Because body control mechanisms limit the amount of ingested vitamin C available to skin, topical application is a good way to target vitamin C directly into skin. Products containing Vitamin C should be protected from light and containers should be closed carefully after each use to delay oxidation (metals like copper accelerate oxidation). Vitamin C is available in a number of forms (e.g. ascorbyl palmitate, tetrahexydecyl ascorbate, magnesium ascorbul phosphate) but each new chemically modified form should be validated, i.e., shown to have actual vitamin C properties in vivo.

Figure. L-Ascorbic acid

Ascorbyl palmitate http://www.skinactives.com/Ascorbyl-Palmitate-Vitamin-C.html Another form of Vitamin C. Esterification of ascorbic acid with a fatty acid (palmitic acid) allows it to do its antioxidant job in the oily phase; it may also help extend the life of ascorbic acid.

Figure. Ascorbyl palmitate Astaxanthin http://www.skinactives.com/Astaxanthin.html Natural astaxanthin, a carotenoid, is a potent antioxidant that enhances the immune system, and reduces the acute inflammation reaction of the skin and underlying tissue that follows excessive exposure to UV radiation. Carotenoids in general, and especially astaxanthin, protect cells against oxidation by quenching singlet oxygen and dissipating the energy as heat, and scavenging free radicals to prevent and terminate chain reactions, complementing the activity of vitamin E which is effective at higher oxygen concentrations. Due to its particular molecular structure, astaxanthin serves as an extremely powerful antioxidant. It has a very effective quenching effect against singlet oxygen, a powerful scavenging ability for lipid and free radicals and effectively breaks peroxide chain reactions. Astaxanthin has also been shown to enhance and modulate the immune system. These effects in combination or separately may reduce the acute inflammation reaction of the skin and tissue just beneath the skin that follows excessive exposure to UV radiation. The astaxanthin used in SAS products is purified from the microalgae H. pluvialis, grown and processed in Hawaii.

Figure. Astaxanthin

Figure. Haemotococcus pluvialis (Chlorophyceae). Astragalus extract http://www.skinactives.com/Astragalus-Extract.html Radix Astragali, the root of the astragalus plant, has been used in traditional Chinese medicine as Huang Qi (Huangqi) for over 2,000 years. It is still used to enhance the immune system, to protect the body against stress and aid with skin healing. One of the active chemicals in Astragalus is astragaloside IV, shown to have antiviral and anticancer properties. SAS Astragalus root extract is standardized and contains at least 10% of astragaloside IV. Other active chemicals in this plant extract include flavonoids, saponins, polysaccharides, amino acids, and trace elements.
Sevimli-Gur, C., Onbasilar, I., Atilla, P., Genc, R., Cakar, N., Gurhan, I., Bedir, E. (2011) In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus. J. Ethnopharmacology, 134: 844-850

Figure: Astragalus propinquus (syn. Astragalus membranaceus) a.k.a. hung q

Azeloyl glycine http://www.skinactives.com/Azeloyl-Glycine.html

Azeloyl glycine normalizes sebum production, and has activity as antimycotic, antiacne, and skin lightener.
Rigano, L.; Cucchiara, M (2003) Azeloyl - glycine : a new active in skin disequilibrium. Applied Cosmetology, 21: 177-188.
O HO 2 C CH 2 NH C (CH 2 ) 7 O C NH CH 2 CO 2 H

Journal of

Figure. Azeloyl glycine. Go to top

B Babassu oil This oil is extracted from the seeds of the Babassu (Attalea speciosa ) palm, which grows in the Amazon. The oil is similar in appearance and composition (rich in lauric and myristic fatty acids) to coconut oil, i.e. solid at room temperature but melting in contact with the skin.

Figure: Babassu palm (Attalea speciosa)

Baicalin from Scutellaria baicalensis http://www.skinactives.com/Baicalin-Scutellaria-Baicalensis.html Skullcap is one of the key herbs in Chinese medicine with the name hung qn. Skullcap extract contains baicalein, chrysin and more but SAS powder extract is standardized for the flavonoid baicalin (90%). For the skin, the most relevant activities of baicalin are prevention of damage by UV and control of atopic dermatitis but also seems to have anticancer and antiviral activity.
Wei, M., Bingjiang, L., Dan, L. (2010) Baicalin protects human fibroblasts against Ultraviolet A induced oxidative damage and photoaging in vitro. J. Inv. Dermatology, 130: S133-S133

Min, Wei, Lin, Xiang-Fei, Miao, Xu, Wang, Bao-Tao, Yang, Zi-Liang, Luo, Dan. (2008) Inhibitory effects of baicalin on ultraviolet B-induced photo-damage in keratinocyte cell line. 36: 745-760. Note: Skullcap extract is used in products from La Prairie, Clinique and MLab.

Figure. Baicalin Bearberry (Arctostaphylos Uva-Ursi) http://www.skinactives.com/Bearberry-Extract-Uva-Ursi.html An amazing array of beneficial chemicals make Arctostaphylos Uva-Ursi (Latin for bearberry) a veritable pharmacy, with arbutin (inhibitor of melanin synthesis - also sold pure), allantoin (antiinflammatory, antioxidant, keratolytic - also sold pure), betulinic acid (skin lightener, anti-cancer - also sold pure), ellagic acid (cancer preventive - also sold pure), lupeol (antioxidant, antiinflammatory), gallic acid (antibacterial), ursolic Acid (anti-cancer) and many more.

Figure. Bearberry Benzoyl peroxide (BP) is very effective in killing Propionibacterium acnes, and it has some (minimal) effect on microcomedo formation. BPO will often cause erythema (redness of the skin produced by congestion of the capillaries), scaling and, sometimes, contact sensitivity. Because free radicals can damage DNA, leading to mutations, benzoyl peroxide is also carcinogenic. Possible alternatives: retinoids will do a much better job of preventing the formation of microcomedos and there is a large number of ingredients that will kill P. acnes, among them Coleus forskholii and tea tree essential oils.

Figure. Benzoyl peroxide.

The oxygen-oxygen bond in peroxides is weak, so benzoyl peroxide breaks down forming free radicals. [C6H5C(O)]2O2 2 C6H5CO2 That tiny little dot is what makes benzoyl peroxide bad for your skin: it says that the product of its breakdown is a free radical. Beta carotene This is a terpenoid (hydrocarbon) strongly-colored red-orange pigment abundant in plants and fruits, and a precursor of vitamin A. Mordehay Avron (a dear friend of HNS, gone some years back) started a new industry: the purification of high quality chemicals of medical and nutritional importance obtained from microalgae cultured in tanks. Avron's basic research in the unicellular alga Dunaliella bardawil (a.k.a. D. salina), led to successful industrial applications. A new industry emerged which produces and markets -carotene for its anti-cancer activity, with cis-isomers from natural sources such as Dunaliella shown to be more effective than the all-trans form as anti-cancer agents. We at Skin Actives Scientific are very proud to offer high quality antioxidants manufactured in Israel using the advanced technology started by Mordehay Avron and his colleagues.

Figure. Beta carotene.

Beta glucan (oat) http://www.skinactives.com/Beta-Glucan-from-Oat.html Many organisms make beta glucans, i.e. sugars linked to each other by beta 1,3 glycosidic bonds. The beta glucan from oat is anti-inflammatory
Note: in Aveeno products.

Figure. Avena sativa (oat).

Beta glucan (yeast)

http://www.skinactives.com/Beta-Glucan-Yeast.html This polysaccharide is similar in structure to the glucan in Maitake mushroom. The cell wall of yeast is very complex , with a structure that is still being studied and seems to include beta(1--> 3)-glucan, beta(1--> 6)-glucan, chitin, and mannoprotein. Apparently, the effect of these carbohydrates on our immune system is innate, i.e. present in our genetic make-up. When we come in contact with these very special carbohydrates, our immune system seems to activate so that, when we come in contact with a pathogen, we are better able to deal with it and stop an infection. Apparently, this response may also prepare us to stop our own "gone bad" cells, those that have lost the capacity to control cell division and have become cancer cells. A great advantage to allergy sufferers: yeast beta glucan (and beta glucans from other fungi) seems to decrease the tendency to allergic responses and inflammation. As an added bonus, it tightens the skin.
Note: The orientation of a linkage (as alpha or beta) changes the properties of the resulting oligo o polysaccharide. Starch, for example, has glucose monomers linked to each other in alpha linkages. Conversely, cellulose has them linked in beta. We can digest starch but cant digest cellulose.

Figure. Examples of beta glycosidic linkages. Betulinic acid http://www.skinactives.com/betullinic-acid.html Betulinic acid (from Betula alba extract) stimulates collagen synthesis and inhibits the enzyme elastase, preventing and correcting the loss of elastic fibers responsible for skin suppleness, improves skin color. Betulinic acid is also a selective inhibitor of melanoma that works by inducing apoptosis of cancer cells.

Figure. Betulinic acid. Bilberry Fruit Extract (Vaccinium) http://www.skinactives.com/Bilberry-Vaccinium-Fruit-Extract.html Our extract is standardized for anthocyanins (25%) which give this extract a gorgeous color, this extract has vasoprotective, anti-inflammatory, antioxidant and healing activity. Anthocyanins, from bilberry and many other species, have also been shown to have anti-aging and anti-cancer properties.

Figure. Bilberry.
Bae, Ji-Young; Lim, Soon Sung; Kim, Sun Ju, Choi, Jung-Suk (Park, Jinseu; Ju, Sung Mi; Han, Seoung Jun; Kang, Il-Jun, Kang, Young-Hee (2009) Bog blueberry anthocyanins alleviate photoaging in ultraviolet-B irradiation-induced human dermal fibroblasts. Molecular nutrition & food research. 53: 726738.

Bisabolol -(-)http://www.skinactives.com/Bisabolol-alpha.html This natural chemical is an unsaturated monocyclic sesquiterpene alcohol, partly responsible for the anti-inflammatory effect of chamomile essential oil. Bisabolol will not lead to sensitization or allergic reactions. Useful in the treatment of acne, may also help with rosacea. Bisabolol is well absorbed and also facilitates the absorption of other ingredients. When applied to skin that has been damaged by laser treatment, bisabolol increased skin hydration, surface lipids, skin elasticity and decreased TEWL (trans-epidermal water loss, i.e. increased the integrity of the skin barrier). The anti-inflammatory effect of bisabolol is comparable to corticosteroid compounds, with the clear advantage that it lacks the side effects that should make the use of corticosteroids like hydrocortisone or dexamethasone a last resort.

Madhavan, Bindu Nair (1999) Final report on the safety assessment of bisabolol. International Journal of Toxicology, 18(Suppl. 3):33-40. Stanzl, Klaus; Vollhardt, Jurgen. (2001) The case of alpha-bisabolol. Editor(s): Barel, Andre O.; Paye, Marc; Maibach, Howard I. Handbook of Cosmetic Science and Technology, pp.277-284. Jakovlev, V.; Isaac, O.; Thiemer, K.; Kunde, R. (1979) Pharmacological investigations on the components of chamomile. II. New investigation on the antiinflammatory effects of (-)-alpha-bisbolol and bisabolol oxides. Planta Medica, 35:125-40. Yakovlev, V.; Von Schlichtegroll, A. (1969) Antiinflammatory activity of (-)- - bisabolol , an essential component of chamomile oil.. Arzneimittel-Forschung (1969), 19(4), 615-16.

Figure: alpha bisabolol

Black cumin oil (Nigella sativa) oil http://www.skinactives.com/Black-Cumin-Oil.html The use of black cumin oil in Biblical times and in Ayurvedic medicine has been substantiated by the finding of valuable phytochemicals in the seed: alpha spinasterol, campesterol, phytosterols, nigellone, thymohydroquinone, and more. Fatty acids in this oil include linoleic acid (50%), oleic acid (20%), and cis-11,14-eicosadienoic acid (8%). Use to alleviate eczema and to control fungal infection (probably because of its thymoquinone content). Thymoquinone has antineoplasic, chemopreventive activity.This oil has a strong, exotic, aroma.
Aljabre, SHM; Randhawa, MA; Akhtar, N; Alakloby, OM; Alqurashi, AM; Aldossary, A (2005) Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone J Ethnopharmacology 101: 116- 119. Woo, Chern Chiuh, Kumar, Alan Prem; Sethi, Gautam, Tan, Kwong Huat Benny (2012) Thymoquinone: Potential cure for inflammatory disorders and cancer. Biochemical Pharmacology, 83: 443-451 Losso Jack N.; Bawadi Hiba A.; Chintalapati Madhavi (2011) Inhibition of the formation of advanced glycation end products by thymoquinone Food Chemistry, 128: 55-61

Figure. Black cumin (Nigella sativa) Boswellia serrata http://www.skinactives.com/Boswellia-Serrata.html Indian frankincense (a.k.a. Indian olibanum, salai guggul) has been used to alleviate arthritis since biblical times. Our extract of Indian frankincense is standardized for the active triterpenoids, called boswellic acids. Boswellic acids act via inhibition of 5-lipoxygenase, an enzyme that catalyses the two first steps in the oxygenation of arachidonic acid and its conversion into leukotrienes. Leukotrienes are involved in inflammation and hypersensitivity reactions that are important defense mechanisms but have also been implicated as mediators of hypersensitivity reactions and allergic conditions. Boswellic acids also inhibit elastase from leukocytes, an enzyme that in its natural location (in neutrophils) is responsible for degrading foreign material but, when leaked to the surrounding medium, can damage surrounding tissues through proteolysis of elastin. Boswellia serrata promotes collagen synthesis and is also an inhibitor of hyaluronidase (breaks down hyaluronic acid), a real life preserver for the dermal matrix. Use Boswellia serrata extract for its anti-aging and anti-inflammatory activities, it will help preserve the structure of collagen and elastin and promote collagen synthesis.

Huang, Mou-Tuan; Badmaev, Vladimir; Ding, Yu; Liu, Yue; Xie, Jian-Guo; Ho, Chi-Tang. (2000) Antitumor and anti-carcinogenic activities of triterpenoid, -boswellic acid. BioFactors (2000), 13: 225-230. Ammon HP., Safayhi H., Mack T., Sabieraj J. (1993) Mechanism of antiinflammatory actions of curcumine and boswellic acids. J Ethnopharmacol., 38:113-9. Calzavara-Pinton, P, Zane, C, Facchinetti, E. , Capezzera R., and Pedretti, A.(2010) Topical Boswellic acids for treatment of photoaged skin. Dermatological Therapy, 23, Suppl. 1:S28-S32 Note: This extract has been popularized as Boswelox by LOreal and its Wrinkle-de-crease

Figure. Boswellia serrata

Bupleurum Falcatum root extract http://www.skinactives.com/Bupleurum-Falcatum.html This extract, use in Chinese medicine for millennia, has anti-cellulite, anti-inflammatory, antihistaminic properties. The saikosaponins in Bupleurum falcatum are mainly responsible for the plant's medicinal activities, but the pectins in this root extract also have immune system modulation activity. In vitro studies indicate saikosaponins have antiinflammatory effects by inhibiting arachidonic acid metabolism. Saikosaponin-d has immunoregulatory activity by promoting interleukin-2 production and receptor expression as well as modulating T-lymphocyte function.
Leung, Chung Yee; Liu, Liang; Wong, Ricky N. S.; Zeng, Yao Ying; Li, Ming; Zhou, Hua. (2005) Saikosaponin-d inhibits T cell activation through the modulation of PKC theta , JNK, and NF- kappaB transcription factor. Biochemical and Biophysical Research Communications, 338:1920-1927. Matsumoto, Tsukasa; Hosono-Nishiyama, Kanako; Guo, Ying-Jie; Ikejima, Takashi; Yamada, Haruki. (2005) A possible signal transduction pathway for cyclin D2 expression by a pectic polysaccharide from the roots of Bupleurum falcatum L. in murine B cell. International Immunopharmacology,5:1373-1386. Kato, Masashi; Pu, Mei-Yi; Isobe, Ken-Ichi; Iwamoto, Takashi; Nagase, Fumihiko; Lwin, Tint; Zhang, Yue-Hua; Hattori, Taku; Yanagita, Noriyuki; Nakashima, Izumi. (1994) Characterization of the immunoregulatory action of saikosaponin-d. Cellular Immunology 159:15-25. Park, Kwan Ha; Park, Jongmin; Koh, Dongsoo; Lim, Yoongho. (2002) Effect of Saikosaponin A, a triterpenoid glycoside, isolated from Bupleurum falcatum on experimental allergic asthma. Phytotherapy Research, 16: 359-363.

Matsumoto, Tsukasa; Yamada, Haruki. (1995) Regulation of immune complexes binding of macrophages by pectic polysaccharide from Bupleurum falcatum L.: pharmacological evidence for the requirement of intracellular calcium/calmodulin on Fc receptor up-regulation by bupleuran 2IIb. Journal of Pharmacy and Pharmacology 47:152-6.

Figure. Bupleurum falcatum

Butchers broom (Ruscus aculeatus L.) http://www.skinactives.com/Butcher-s-Broom.html

Butchers broom (Liliaceae, Box-Holly), is not very new for the users of our capillary health cream, but we responded to the request by DIY clients who like to use this very valuable active in their own potions. This extract helps with venous insufficiency, and decreases capillary permeability. Our extract is standardized for ruscogenins.
Vanscheidt, Wolfgang; Jost, Volker; Wolna, Peter; Lucker, Peter W.; Muller, Alfred; Theurer, Christoph; Patz, Brigitte; Grutzner, Karen I. (2002) Efficacy and safety of a Butcher 's broom preparation ( Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency. Arzneimittel-Forschung, 52: 243-250. Capra, C. (1972) Pharmacology and toxicology of some components of Ruscus aculeatus. Fitoterapia, 43: 99-113. Facino, Roberto Maffei; Carini, Marina; Stefani, Rita; Aldini, Giancarlo; Saibene, Luisella. (1995) Antielastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus : factors contributing to their efficacy in the treatment of venous insufficiency Archiv der Pharmazie, 328: 720-4.

Figure. Ruscus aculeatus

Go to top C Caffeine http://www.skinactives.com/Green-Tea-Extract-with-Caffeine.html Caffeine decreases the risk of skin cancer promoted by UV irradiation; apparently by slowing down repair of DNA mutations caused by UV making it more precise and preventing mutations that may lead to cancer. Caffeine also decreases the thickness of subcutaneous fat layer by inducing lipolysis Topical application of caffeine is safe, as shown by its use to facilitate breathing of newborns. Other beneficial effects of caffeineare analgesia, antiviral, antidermatitis, antioxidant. The de-puffing effect of caffeine may be mediated by the promotion of sodium export from the cell, which is followed by water loss.

Calcium Pantothenate, vitamin B5 http://www.skinactives.com/Calcium-Pantothenate-Vitamin-B5.html Pantothenic acid is a component of coenzyme A, required in synthesis of fatty acids and sphingolipids, components are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity. Even when following a normal healthy diet, topical application of pantothenic acid may help prevent acne, alleviate allergic reactions, help with skin healing and prevent to some extent the damage to the skin caused by radiation therapy.

Figure. Pantothenic acid.

Leung L (1995). "Pantothenic acid deficiency as the pathogenesis of acne vulgaris". Med Hypotheses 44: 4902. Szorady, I.; Horvath, E.; Toth, E. (1966) Antihistamine action of pantothenic acid Internationale Zeitschrift fuer Vitaminforschung , 36:126-33.

L-Carnitine (acetyl) http://www.skinactives.com/L-Carnitine-Acetyl.html L-Carnitine, a derivative of the amino acid lysine, carries activated fatty acids through the mostly impermeable inner mitochondrial membrane, allowing the respiration of fatty acids. The activated fatty acid (acyl-CoA) cannot pass through the membrane but there is a special translocator for acyl-carnitine. Once carnitine releases the fatty acid it carries (a process involving a tranferase), carnitine can go out again and take up another activated fatty acid. Carnitine was initially believed to be a vitamin, and called vitamin BT, but humans can synthesize L-carnitine, although under certain conditions and depending on the diet the demand for L-carnitine may exceed an individual's capacity to synthesize it, making it a "conditionally essential nutrient". Some new information suggests that ingesting carnitine in excess may be problematic for heart disease, but this is only for orally taken carnitine.

Carnosine (Acetyl L-) http://www.skinactives.com/L-Carnosine.html This natural peptide also has a relatively new trade name, Beta Alistine, but research into its beneficial effects on healing goes back to the 1980s. Carnosine accelerates and improves healing, it also prevents cross-linking of collagen and other proteins in the dermis, one of the causes of wrinkles and loss of elasticity brought about by aging and exposure to UV (sunlight). Carnosine is also an antioxidant and seems to improve the immune response. Catalase Catalase is an enzyme that converts hydrogen peroxide into water and oxygen. It is important to add catalse (or lactoperoxidase) to any skin care product that contains superoxide dismutase.

Figure. Ribbon model of catalase. Koepke, Jay I., Wood, Christopher S., Terlecky, Laura J., Walton, Paul A., Terlecky, Stanley R. (2008) Progeric effects of catalase inactivation in human cells. Toxicology and Applied Pharmacology, 232: 99108

Centella asiatica (Gotu kola, a.k.a. Hydrocotyle asiatica). http://www.skinactives.com/Centella-Asiatica.html This oriental herb has been used for centuries in both traditional Chinese and Indian medicine. The active chemicals in the extract are terpenoids including asiatic acid, madecassic acid, and asiaticoside. Centella asiatica helps wound healing, apparently by stimulating the production of type I collagen and decreasing the inflammatory reaction and myofibroblast production. Triterpenes from gotu cola may also affect various stages of tissue development including keratinization (the process of replacing skin after sores or ulcers) and stimulate the formation of lipids and proteins necessary for healthy skin. The triterpenes of Centella asiatica are also reported to increase the incorporation of alanine and proline into the structure of collagen, promoting healing of epithelial ulcers, bedsores and skin disorders. Recent studies have shown Centella asiatica may have a positive effect on the circulatory system and may improve blood flow throughout the body by strengthening the veins and capillaries.
Note: Active ingredient in Murad, Creme de la Mer, Dermadoctor. Bonte, F.; Dumas, M.; Chaudagne, C.; Meybeck, A. (1995) Asiaticoside and madecassoside comparative activities on human fibroblast type I and III collagen secretion. Annales Pharmaceutiques Francaises, 53:38-42. Tenni, R.; Zanaboni, G.; De Agostini, M. P.; Rossi, A.; Bendotti, C.; Cetta, G. (1988) Effect of the triterpenoid fraction of Centella asiatica on macromolecules of the connective matrix in human skin fibroblast cultures. Italian Journal of Biochemistry, 37:69-77. Cesarone M R; Laurora G; De Sanctis M T; Incandela L; Grimaldi R; Marelli C; Belcaro G (1994) The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study. Minerva angiologica. 42: 299-304.

Ceramides Ceramides are a family of lipid molecules consisting of a long-chain or sphingoid base linked to a fatty acid via an amide bond. This polar lipid will enhance skin moisturization and skin protection, ultimately helping to repair sensitive and dry skin. Use ceramides if you want to prevent skin roughness and increase skin hydration. Ceramides are found in high concentrations within the cell membrane of cells, but they have more than a structural role. They are signaling molecules involved in the regulation of cellular differentiation, proliferation, and apoptosis. Some ceramides inhibit cancer cell growth. For more information, see our article on Ceramides in this SAS newsletter (April 2012) http://us1.campaign-archive1.com/?u=275e0909c6eb9b02d2d58bce2&id=830ce10fff Cholecalciferol

Cholecalciferol is a form of vitamin D3. A good active to use for psoriasis, dry (xerotic) skin and flakiness, vitamin D3 is also photoprotective; it will help skin damaged by chemotherapy and skin that tends to heal forming hypertrophic scars. Cholecalciferol is very sensitive to UV radiation so use it in night creams. Chrysin http://www.skinactives.com/Chrysin.html One of the causes of infra-orbital shadows (dark circles) is the accumulation of hemoglobin and its colored degradation products (biliverdin, bilirubin and iron) in the dermis and epidermis. Chrysin, a flavone present in blue passion flower (Passiflora cerulea) activates the enzyme uridine diphosphate-glucuronosyltransferase (UGT1A1) that leads to the degradation of bilirubin, helping with stubborn dark under-eye circles. It also has anti-cancer activity plus antiinflammatory activity through the suppression of cyclooxygenase-2.
Walle, U. K. Walle, T. (2002) Induction of human UDP-glucuronosyl transferase UGT1A1 by flavonoids-structural requirements. Drug Metabolism & Disposition 30:564-569. Woo, Kyung Jin; Jeong, Yong-Jin; Park, Jong-Wook; Kwon, Taeg Kyu. (2004) Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochemical & Biophysical Research Communications, 325:1215-1222.

Figure. Chrysin. Coconut endosperm http://www.skinactives.com/Coconut-Endosperm-Kinetin.html Everything the coconut embryo needs to grow and develop has to come from inside the fruit, because it is isolated from the outside world by a thick cover. Everything needed for growth and development of the embryo, i.e. amino acids, sugars, vitamins and growth factors (like kinetin) are present in the liquid called coconut water or milk. This fact has been know for a long time and this is why when scientists want to grow plant cells in Petri dishes they use coconut milk as a

growth medium. The coconut endosperm we use at Skin Actives is dried by lyophilization (i.e. dried at low temperature) to avoid loss of activity of labile components. Coenzyme Q10 http://www.skinactives.com/Coenzyme-Q10.html Also called ubiquinone, the "ubiquitous quinone" because it is present in plants and animals, including the human skin. This is a crucial molecule in respiration. Its topical application restores mitochondrial activity, increasing energy production as ATP plus reducing power needed to make new collagen. This is the active that many skin care products promise but don't deliver (idebenone was created to offer a less expensive, laboratory version of Co Q10). Antiage, antioxidant (lipophilic). A very stimulating active, it will push your skin into "high gear". CoQ10 has a less intense orange color than Idebenone and has lower allergenic tendencies. We recommend its use instead of Idebenone as much as possible.

Figure. Coenzyme Q10.

Figure. Skin Actives CoQ10. Prahl, S, Kueper, T., Biernoth, T., Woehrmann, Y., Muenster, A., Fuerstenau, M., Schmidt, M., Schulze, C., Wittern, K. -P., Wenck, H., Muhr, G. -M., Blatt, T. (2008) Aging skin is functionally anaerobic: Importance of coenzyme Q(10) for anti aging skin care. Biofactors, 32: 245-255

Coffee Fruit Extract http://www.skinactives.com/Coffee-Fruit-Extract.html Many of us wake up in the morning looking forward to a hot water extract of the roasted seeds from Coffea arabica L., a.k.a. coffee. Coffee fruits are fleshy berries, each containing two seeds which are pressed together so that the inner side of each one is flattened. The coffee beverage is made from the ground, roasted seeds (coffee beans) that are removed from the coffee cherries (a.k.a. coffee berries). When the seeds were collected, the rest of the fruit was usually discarded but now the skin care industry has made the coffee fruit a hot commodity. I think it was a great idea to use the up-to-now discarded coffee fruit, because it contains chlorogenic and caffeic acids (antioxidant, anti-inflammatory), ferulic acid (antioxidant), quinic acid (antioxidant, antiviral), trigonelline (antioxidant, anticancer, antibacterial), proanthocyanidins, caffeine, mannans and arabinogalactans, actives truly beneficial to our skin and our bodies. Our coffee fruit extract is extracted from Kona coffee cherries and comes as a freeze dried

powder. Use very little in a water-based serum or cream, it will go a long way. As for any freezedried extract, please keep tightly closed in a dry cool place.
Note: the active in Revale cream.

Coleus forskohlii oil http://www.skinactives.com/Coleus-forskohlii-Oil.html Coleus forskohlii is a member of the mint and lavender family (Lamiaceae) that has seen centuries of use in Ayurvedic Medicine. Synonyms include C. barbatus Benth., Plectranthus forskohlii Willd., P. barbatus Andr. and P. comosus Willemse. This species is a perennial herb with fleshy, fibrous roots that grows wild in the warm sub-tropical temperate areas of India, Burma and Thailand. In India, the plant is even cultivated for use as a condiment. The essential oil is obtained from the fresh root material by hydrodistillation. One of its many components, sesquiphellandrene, provides a pleasant, woody aroma and is valued for its diverse biological benefits including antimicrobial and anti-inflammatory properties. In vitro, this essential oil was found to effectively inhibit the growth of skin pathogens including: 1) Propionibacterium acnes - a microorganism associated with acne and other skin infections, 2) Staphylococcus aureus - a bacterial strain found in infected wounds and skin eruptions including acne, 3) Staphylococcus epidermidis - a bacterial strain occurring in a variety of opportunistic bacterial skin infections and in acne, and 4) Streptococcus mutans - a bacterial strain associated with the progression of dental caries
Coleus forskohlii in Pharmacognosy: Phytochemistry, Medicinal Plants. Lavoisier Publishing Company, 2nd edition, 1119 pp

Collagen Hydrolizate (a.k.a. natural active peptides) http://www.skinactives.com/Natural-Active-Peptides.html This peptide mix is obtained from a natural source, fish collagen (not suitable for vegetarians). The peptides can be as short as two amino acids, and as long as about 30 amino acids length, up to molecular weight 5,000. Because of their relatively low price, we can add them in concentrations that will ensure not just good copper transport, but also provide the skin the amino acids it needs to make its own collagen and even help the skin retain moisture. This is one of the few animal derived actives we have; plants dont make collagen, so phytocollagen, a marketing invention, does not exist. Copper Peptide http://www.skinactives.com/Copper-Peptide-GHK.html

Copper ion (Cu++) has affinity for proteins, a property that is the basis for a traditional method to measure protein concentration. The N-terminal sequence of human albumin (Asp-Ala-HisLys) is the site for the transport of copper ion in the bloodstream. Tight binding also occurs when histidine is in position 2, like in the naturally occurring copper (II) complex of Gly-His-Lys. The peptide Gly-His-Lys, bound or unbound to copper, has been used in skin care as an anti-age active. Because of the widespread use of these formulations, I thought it would be interesting to go back to the original papers (1988-1992) that originated this practice and re-evaluate the evidence. When added to a culture of human fibroblasts, Gly-His-Lys-copper induced a specific, concentration-dependent stimulation of collagen synthesis (Maquart et al. 1988). The concentrations studied were between picomolar and nanomolar (when moles are expressed in grams per volume, the numbers are given in parts per million). A later study (Wegrowski et al. 1992) showed a dose-dependent, biphasic, stimulation of glycosaminoglycan synthesis, (heparan sulfate and dermatan sulfate) in cultures of human skin fibroblasts. Biphasic means that the effect was stimulatory at very low concentrations decreasing towards control levels at higher (but still pretty low) concentrations. The very low concentrations used were chosen because they were at orders of magnitude similar to those measured in vivo. It is interesting that the studies on cell cultures (1988, 1992) dealt with experiments on the effect of copper peptide at concentrations in the order of picomolar (-10M), finding that higher concentrations (still minute, like 10-8M) were not beneficial. Moreover, at higher concentrations copper peptide seems to promote protein breakdown (Allen 2001). For unknown reasons, clinical studies used much higher concentrations, e.g. 0.4%. Not surprisingly, copper peptide at those high concentrations did not help with healing (Bishop et al. 1992). Looking back at these studies, it is clear (at least to me) that copper peptide should not be used at high concentrations. In popular parlance, skin laxity and other bad results attributed to the use of copper peptide have been called the uglies. At Skin Actives Scientific we sell our copper peptide as a dilute solution, that when added to a cream or serum will result in optimal concentrations that benefit the skin. For clients who used other brands of skin care containing copper at high concentrations, I suggest that they abstain from using copper peptide for a few months.
Maquart, Francois Xavier; Pickart, Loren; Laurent, Maryvonne; Gillery, Philippe; Monboisse, Jean Claude; Borel, Jacques Paul. (1988) Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-copper(2+). FEBS Lett. 238:343-6. Wegrowski, Y, Maquart, FX; Borel, JP (1992) Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidylLysine-Cu2+ Life Sciences, 51 : 1049-1056 Bishop, JB; Phillips, LG; Mustoe, TA; VanderZee, AJ; Wiersema, L; Roach, DE; Heggers, JP; Hill Jr, DP et al (1992). "A prospective randomized evaluator-blinded trial of two potential wound healing agents for

the treatment of venous stasis ulcers". J Vasc Surg 16 (2): 251257 Allen, G. (2001) Specific protein degradation by copper(II) ions. In: Probing of proteins by metal ions and their low molecular weight complexes. Book Series: Metal ions in Biological systems. Volume: 38, pp. 197-212

Creatine Pyruvate http://skinactives.com/products/creatine.htm Creatine is a molecule involved in energy use and transfer. Humans can make it, but after a certain age, our skin does not make enough of almost anything, and addition of creatine topically will be welcome. Pyruvate is the other part of this active, and will contribute a little bit of extra energy and building blocks. Be ready to read a lot of hype about a new combination for skin hyperpigmentation: creatine with carnitine will be promoted as a replacement for hydroquinone, but dont get caught in the hype. Our other actives for hyperpigmentation (find them all together in our skin brightening cream) are likely to be better when it comes to skin lightening. But the actives are good and you lose nothing by trying.

Figure. Creatine

Cyanocobalamin (vitamin B12) In our anti-inflammatory cream.

Vitamin-B(12) is a generic term for corrinoid compounds that exhibit the biological activity of cyanocobalamin and are collectively referred to as cobalamins (methylcobalamin and 5deoxyadenosylcobalamin are the active cobalamins in human metabolism). Cobalamin plays a crucial role in the maintenance of homocysteine and methylmalonyl-CoA homeostasis and is required for DNA synthesis. Deficiency of this vitamin is relatively common, a leads to skin or mucous membranes problems.

Figure. Cyanocobalamin Go to top D Dead Sea salts and mud. There is a perfect combination of minerals that will benefit the skin and help alleviate psoriasis. This perfect combination includes, in certain proportions, chloride, magnesium, calcium, bromide, sodium, potassium, strontium, sulfate, lithium and other minerals. How do we know that this is a perfect combination? If you like old stories (like I do) there is one legend that says that, at the command of Cleopatra, considered the most beautiful woman in the antique world, pharmaceutical and cosmetic factories were built near the Dead Sea (their remains can still be seen today at Ein Bokek and Ein Gedi in Israel). If you are a skeptic when it comes to old tales, you still have to believe the barrage of scientific studies showing that Dead Sea salts, brine and mud have greatly beneficial effects on the skin that can be actually seen and measured. There is strong scientific evidence showing that Dead Sea salts make skin smoother, and improve conditions such as psoriasis, atopic dermatitis, xerosis (dry skin), eczema, and vitiligo; they also enhance the skins immune response. Soaking baths or a mud treatment that includes Dead Sea salts or mud can change the mineral composition of plasma. Dermal respiratory factor a.k.a. Yeast Lysate (Saccharomyces) Extract http://www.skinactives.com/Dermal-Respiratory-Factor-Saccharomyces-lysate.html

There is very little scientific information on the effect of live yeast respiratory factor on inflammation but there is a lot of anecdotal evidence. As example of anecdotal evidence I have to include the bit in Miss Congeniality where Michael Caine (Victor) tells Sandra Bullock (Gracie) how to prepare for the swimsuit competition. Gracie: Hemorrhoid cream? Do you really think they'll be looking that closely? Victor: Its for your eye bags. Because there is so much anecdotal evidence and yeast is such a great source for vitamins and more, I thought we could use it in our cellulite cream. Why would this yeast extract increase respiration? It may work by increasing substrate availability but, much more likely, by supplying coenzymes, cofactors and vitamins.

Figure. Yeast cells

Dimethylaminoethanol (DMAE) http://www.skinactives.com/DMAE-Bitartrate.html DMAE improves the firmness of the skin and helps reduce the visual appearance of sagging skin, although the mechanism of action is unknown. It is an amine-based alcohol, a precursor to the neurotransmitter acetylcholine, present in nerve tissue in small amounts and more abundant in fish. DMAE acts as a free radical scavenger due to the high electron content of its nitrogen atom. Once phosphorylated, DMAE is incorporated into the membrane of cells, protecting against the cell membrane protein cross-linking. In addition, DMAE is an immediate precursor to choline, which is involved in cell membrane biosynthesis. We sell DMAE as DMAE bitartrate, a salt

(DMAE is strongly alkaline and hazardous to ship and manipulate), so take into account that the actual percentage of DMAE by weight in the salt is about 37%. For 3% DMAE in 4 oz (120mL) you will need about 10 gm DMAE bitartrate (the rest will be the tartaric acid).

Figure. DMAE

Diosgenin (See also Elixir 10) Leger, D. Y.; Liagre, B.; Corbiere, C.; Cook-Moreau, J.; Beneytout, J.-L. (2004) Diosgenin induces cell cycle arrest and apoptosis in HEL cells with increase in intracellular calcium level, activation of cPLA2 and COX-2 overexpression. International Journal of Oncology, 25 : 555562. Corbiere, C.; Liagre, B.; Terro, F.; Beneytout, J.-L. (2004) Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells. Cell Research, 14: 188-196.

Docosahexanoic acid (DHA) Our DHA rich extract is obtained from an algae culture, Schyzochitrium, an alga related to the Diatoms.

Figure. Docosahexanoic acid indicating the numbers for the carbons counting from the carboxylic acid group (1) or from the omega carbon at the other side of the chain. E

Elixir 10
http://www.skinactives.com/Elixir10-Phytoestrogen-Booster.html

The new SAS Elixir10 booster is a mix of beneficial botanical extracts that can supply your skin (and scalp) with beneficial chemicals that will bind to the estrogen receptors left vacant by menopause. Phytoestrogens are plant chemicals that can interact with two of the most important receptors of steroid hormones: the sex hormone-binding globulin and the cytosolic estrogen receptor. The chemical structure of phytoestrogens differs greatly and may seem very different from estradiol, but a part of the molecule is similar enough to human estrogen to fool the receptor. For those who think that maybe Mother Nature made these chemicals for our benefit, think again: they are part of the defense system against fungi. Also, in the 1940s, it was noticed that pastures of red clover, a phytoestrogen-rich plant, had effects on the fecundity of grazing sheep. It is likely that these plants evolved the biochemical pathways required to make these secondary metabolites to disrupt the hormonal balance in their predators, decreasing birth rates in sheep or whatever animal was having them for breakfast. For our Elixir10, we are using botanical extracts standardized for chemicals with estrogenic properties. As a bonus, many of these chemicals have other beneficial properties, including antioxidant and anticancer activities, and protection from UV damage. Please note that the beneficial properties enumerated below are on top of the estrogenic properties. Ingredients: Soybean (Glycine max) Genistein, Flax (Linum usitatissimum) Lignans, Wild Yam Diosgenin, Soybean (Glycine max) Daidzein, Liquorice (Glycyrrhiza glabra) extract, Luteolin, Resveratrol, Apigenin, Phloretin, Kudzu (Pueraria lobata) Puerarin.

Kudzu Puerarin. Pueraria is a rejuvenating folk remedy in Thailand, a tradition passed on from generation to generation. The Thai name is White Kwao Krua or Kwao Keur. Besides puerarin, the 8-C-glucoside of daidzein, kudzu contains other phytoestrogens, like miroestrol, deoxymiroestrol, daidzin, genistein, and coumestrol. Genistein and daidzein stimulate the synthesis of hyaluronic acid. Genistein induces collagenation in soft tissue wound healing and inhibits tyrosine kinase. Flax lignans are a class of phytoestrogens with antioxidant and cancer-preventing properties, and their skin strengthening properties will help preven scarring and stretch marks and with antioxidant and skin strengthening and cancer-preventing properties. Flaxseed is also used for acne, symptoms of menopause, and breast pain. It is also an anti-inflammatory that helps with eczema, psoriasis. Daidzein activates all three peroxisome proliferator-activated receptors (PPAR) isoforms, a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes, cellular differentiation, development, and metabolism.

Luteolin - A flavonoid with great properties: protection against lipid peroxidation and protease activation by UV radiation, anti-age, anti-itch, anti-inflammatory. We will soon start selling this active individually. Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic antioxidant found in grapes and red wine, blocks UVB-mediated activation of the factor NFkappa-B, and this is the mechanism of protection against photocarcinogenesis. Plant polyphenols like resveratrol may benefit the skin with anti-inflammatory and wound healing activity through their interaction with growth factor receptors (and the cytoplasmic and nuclear pathways these receptors control) besides direct antioxidant activity. Apigenin is a phenolic flavonoid found in chamomile and many other plants. This antioxidant has anti-inflammatory, chemopreventive activity against skin cancer and prevents UVA and B induced skin cancer. It may also help prevent skin aging by UV through inhibition of metalloproteinases. Apple Phloretin is a nice antioxidant and inhibits elastase activity. Phloretin has been shown to inhibit proliferation of breast cancer cells. Wild yam diosgenin.

Brincat, M. P.; Baron, Y. Muscat; Galea, R. (2005) "Estrogens and the skin." Climacteric, 8(2), 110-123 Ellagic acid http://www.skinactives.com/Ellagic-Acid.html This polyphenol has chemopreventive and antioxidant activity. It also works as a skin lightener because it inhibits melanocyte proliferation and suppresses melanin synthesis induced by UV.

O OH O HO OH O HO O

Tachibana, Shinichi; Tanaka, Yoshimasa. Inhibitory effect of ellagic acid on melanogenesis. Fragrance Journal (1997), 25(9), 37-42. Yoshimura, Mineka; Watanabe, Yuko; Kasai, Kouichi; Yamakoshi, Jun; Koga, Takuro (2005) Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation. Bioscience, Biotechnology, and Biochemistry, 69: 2368-2373.

Lesca, P (1983) Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice. Carcinogenesis , 4: 1651-3.

Epidermal Growth Factor (EGF) http://www.skinactives.com/Epidermal-Growth-Factor-BT-EGF.html What is a growth factor? Growth factors, a.k.a. citokines, are naturally occuring proteins capable of stimulating cellular proliferation and cellular differentiation. Growth factors bind to specific receptors on the cell surfaces and are important for the regulation a variety of cellular processes. Among the practical uses of EGF are its use in accelerating healing of skin and cornea. EGF was the first growth factor to be discovered and studied, but many more factors have been found since then. These growth factors differ in size and structure, affecting different receptors and types of cells as a consequence, and causing various effects on the target cells. Application of EGF to the skin will accelerate healing and it will increase the rate of skin renewal of aging skin. In 1986, Stanley Cohen received the Nobel Prize for his work elucidating the role of the Epidermal Growth Factor (EGF) in the regulation of cell growth and development. EGF is a growth factor that plays an important role in the regulation of cell growth, cell proliferation and differentiation. As with all growth factors, it is a small protein. EGF acts by binding to specific receptors on the cell surface, starting a cascade of very organized molecular events, including increased intracellular calcium concentration, energy production and protein synthesis. This is one the specialty proteins made by Skin Actives Scientific using biotechnology. Biotechnology is a short name for an array of sophisticated methods that allow scientists to make large amounts of a single protein, nearly pure and fully active, at a fraction of the cost of extracting it from the original source material. Please note that our growth factors are sold for use in cosmetics only.
Heck, Diane E.; Laskin, Debra L.; Gardner, Carol R.; Laskin, Jeffrey D. (1992) Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. J Biol Chem 267:21277-80. Tsang, Man Wo; Wong, Wan Keung R.; Hung, Chi Sang; Lai, Kwok-Man; Tang, Wegin; Cheung, Elaine Y. N.; Kam, Grace; Leung, Leo; Chan, Chi Wai; Chu, Chung Min; Lam, Edward K. H. (2003) Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care, 26:1856-1861. Grahn, Jennifer C.; Isseroff, R. Rivkah. (2004) Human melanocytes do not express EGF receptors. Journal of Investigative Dermatology, 123: 244-246. Cohen, Stanley (1993). Nobel Lecture 1986. Epidermal Growth Factor. In: Physiology or Medicine 19811990: Nobel Lectures, Including Presentation Speeches and Laureates Biographies, T. Frangsmyr and J. Lindsten (eds.) World Scientific Pub Co Inc (May 1993) pp 333-345.

Epigallocatechin gallate (EGCG) from green tea http://www.skinactives.com/Green-Tea-Extract-with-EGCG.html The polyphenols in green tea are responsible for some of its remarkable medicinal properties. These include (+) catechin (C), (+) gallocatechin (GC), (-) epicatechin (EC), (-) epigallocatechin (EGC) and (-) epigallocatechin gallate (EGCG). Our green tea extract is standardized for EGCG, i.e. it has been enriched to ensure a very high concentration of this particular chemical, but some of the other beneficial chemicals remain. EGCG has been shown to prevent UV caused cancerous and non-cancerous skin tumors. It has been suggested that chemopreventives like EGCG, slow down DNA repair that follows damage produced by UV irradiation and, by slowing it down, allow the repair to be more precise, avoiding the mutations that lead to cancer. EGCG is also an effective antioxidant, and scavenging of OH radicals could be another mechanism for its anticancer properties.

Figure. EGCG
Lu, Yao-Ping; Lou, You-Rong; Xie, Jian-Guo; Peng, Qing-Yun; Liao, Jie; Yang, Chung S.; Huang, MouTuan; Conney, Allan H. (2002) Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proceedings of the National Academy of Sciences USA: 99(19), 12455-12460. Huang, Chieh-Chen; Fang, Jai-You; Wu, Wen-Bin; Chiang, Han-Sun; Wei, Yuan-Ju; Hung, Chi-Feng (2005) Protective effects of (-)-epicatechin-3-gallate on UVA-induced damage in HaCaT keratinocytes. Archives of Dermatological Research: 296(10), 473-481. Hsu, S.; Yamamoto, T.; Borke, J.; Walsh, D. S.; Singh, Baldev; R., Sushma; T., Kamatani; Nah-Do, N.; Lapp, C.; Lapp, D.; Foster, E.; Bollag, W.B.; Lewis, J.; Wataha, J.; Osaki, T.; Schuster, G. (2005) Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14. Journal of Pharmacology and Experimental Therapeutics: 312(3), 884-890.

Fujiki, Hirota; Suganuma, Masami; Okabe, Sachiko; Sueoka, Eisaburo; Suga, Kenji; Imai, Kazue; Nakachi, Kei; Kimura, Shunsaku (1999) Mechanistic findings of green tea as cancer preventive for humans. Proceedings of the Society for Experimental Biology and Medicine: 220(4), 225-228.

Essential oils. DO NOT USE DIRECTLY ON THE SKIN. http://www.skinactives.com/Kit-Essential-Oils.html The very volatile molecules in these oils reach the olfactory bulbs in our noses giving us great pleasure. Essential oils are extracted from a variety of plants and contain the volatile chemicals that can be evaporated by water steam. The high price of some essential oils is due to the very low yield, i.e. many pounds of plant material need to be treated to get just a few drops of essential oil. Some of the volatile compounds present in essential oils are terpenes, with the most abundant terpenes being linalol (in the essential oil of lavender), 2-Z-citral (lemongrass), santalenes (sandalwood), patchouli alcohol (patchouli), and geraniol and citronellol (rose). Other terpenes common in essential oils include limonene, menthol and farnesol.
Some examples of essential oils Anise from the fruit of Illicium verum, the star anise. Antibacterial, analgesic and antioxidant, it is used in Chinese medicine and gives its aroma to the Galliano liqueur. Cedarwood essential oil is extracted from the wood of Juniperus virginiana. A powerful antiseptic, fungicidal and anti-seborrhea (helps with dandruff and oily hair). Chamomile. The essential oil of Chamomilla recutita (L.) (also called Matricaria recutita L.), a plant grown mainly in central and eastern Europe, Egypt, and Argentina, may contains up to 50% alphabisabolol. Bisabolol and chamazulene (which is responsible for its deep blue color) contribute to the antiinflammatory properties of genuine chamomile oil. Eucalyptus, from the wood and leaves of Eucalyptus globulus. Analgesic, anti-bacterial, antiinflammatory, antiseptic, antiviral.

Lavender (Lavandula sp.) extract and essential oil Lavender beautiful scent is theusual reason for using it, but its leaves also contain chemicals with antiseptic, antibacterial and analgesic properties, like camphor and cinnamaldehyde. Lemonbalm, Mint Balm, Melissa, Sweet Balm (Melissa officinalis) essential oil Antiinflammatory (probably by inhibiting hyaluronidase), antimicrobial, antiviral, antifungal, helps with healing and itching, antioxidant. Contains valuable chemicals like rosmarinic, ursolic and caffeic acids and luteolin Lemongrass (Cymbopogon citratus) oil http://www.skinactives.com/Lemongrass-Essential-Oil.html This essential oil, obtained usually by steam distillation, has antifungal activity, and can be used against dermatophytes. Contains monoterpene citral as the major constituent (75%) which finds

uses as flavouring agents, and in perfumery and pharmaceutical industry and as a natural precursor of semisynthetic vitamin A Peppermint from the leaves of Mentha arvensis. Antimicrobial and lovely aroma. Sage from the leaves of Salvia lavandulifolia. Anti-inflammatory, antiseptic and astringent. Sandalwood essential oil This very expensive essential oil is the only known source of alphasantalol. This skin cancer chemopreventive agent induces apoptotic death of human epidermoid carcinoma A431 cells via caspase activation. Ylang Ylang from the petals of Cananga odorata flower. Use it just because it smells beautiful! 4-ethoxybenzaldehyde http://www.skinactives.com/4-Ethoxybenzaldehyde.html Draelos et al. (2005) showed that topical application of this active at a 1% concentration improved uneven skin tone and alleviated rosacea. The mechanism of action may involve inhibition of prostaglandin E2.
Draelos, Z.D. and Fuller, B.B. (2005) Efficacy of 1% 4-ethoxybenzaldehyde in reducing facial erythema Dermatologic surgery, 31: 881-5

F Ferulic acid http://www.skinactives.com/Ferulic-Acid.html Also in our UV repair cream A potent antioxidant, ferulic acid protects skin from UV induced erythema by absorbing UV before it reaches the skin (photoprotective) and by preventing lipid peroxidation and the consequent damage to cell membranes. It has also been shown to have chemopreventive activity, preventing a variety of cancers in different tissues including skin and anti-allergic.
Oka, T., Fujimoto, M.; Nagasaka, R., Ushio, H., Hori, M., Ozaki, H. (2010) Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol, attenuates mast cell degranulation. Phytomedicine, 17, 152-156.

CH

CH

CO 2 H

HO OMe

Lin F-H; Lin J-Y; Gupta R D; Tournas J A; Burch J A; Selim M A; Monteiro-Riviere N A; Grichnik J M; Zielinski J; Pinnell S R (2004) Ferulic Acid Stabilizes a Topical Solution Containing Vitamins C and E and Doubles its Photoprotection for Skin , J Invest Dermatol 125: 826-32. Lesca, P. (1983) Protective effects of ellagic acid and other plant phenols on benzo[alpha]pyrene-induced neoplasia in mice. Carcinogenesis, 4(12), 1651-3.

Flax oil The oil extracted from the Linum usitatissiumum seeds goes rancid rapidly, because it is so rich in unsaturated fatty acids. A typical composition is about 50% triply unsaturated -linolenic acid, less than 10% saturated acids like palimitic acid and stearic acid, 20% of monounsaturated oleic acid and about 15% doubly unsaturated linoleic acid. Flax oil has the highest level of the omega3 fatty acid among vegetable oils.

Figure. Linum usitatissimum (Khlers Medizinal-Pflanzen) Folic acid

Folacin is the generic term for folic acid and related substances having its biochemical activity. Folic acid is a vitamin (group B) because it is required for human metabolism but it cannot be synthesized (humans cannot make PABA or attach glutamic acid to pteroic acid, required to make the folate molecule). Although folic acid is normally mentioned in connection with pregnancy because its deficiency during gestation can lead to serious birth defects, everybody needs it because it is required for DNA synthesis and cell division

Figure. Folic acid. Forskolin http://www.skinactives.com/Cellulite-Control-Cream.html Coleus forskohlii is a plant that has been used since ancient times in Hindu and Ayurvedic traditional medicine. The root portion contains the active constituent, forskolin. Forskolins primary mode of action is to increase cyclic adenosine monophosphate (cAMP) and cAMPmediated functions, via activation of the enzyme adenylate cyclase. For cellulite, the most important role of forskolin is the activation of lipase activity, an enzyme that breaks down fats, but it also has anticancer activity, and promotes nerve repair by increasing cAMP concentrations. We dont sell forskolin by itself because it would need some medical supervision, but you will find this very valuable active in our cellulite control cream.

Fucoidan http://www.skinactives.com/Fucoidan-Brown-Alga-Phaeophyta.html See also Glycan Booster These are sulfated polysaccharides with a structure that depends on the plant source, and growing conditions. Fucoidan applied to the skin will increase the density of collagen bundles, decrease activity of proteases (enzymes that break down dermal proteins), increase scavenging of free radicals, and increase cell proliferation. These effects would be mediated through increased expression of integrin a21 and may also help with wound healing. In addition to assisting in collagen synthesis, fucoidan inhibits the replication of many viruses, including herpes, human cytomegalovirus, HIV-1 and others. Fucoidan has been shown to inhibit the binding of the bacteria Helicobacter pylori (involved in human ulcers) to stomach epithelial cells. The fucoidan we use at Skin Actives is extracted and purified from brown algae (Phaeophyta).
Robert, L.; Fodil-Bourahla, I.; Bizbiz, L.; Robert, A. M. (2004) Effects of L-fucose and fucose-rich oligo- and polysaccharides (FROP-s) on collagen biosynthesis by human skin fibroblasts. Modulation of the effect of retinol, ascorbate and alpha- tocopherol Biomedicine & Pharmacotherapy, 58 : 65-70.

Fucoxanthin is a xanthophyll, is found as an accessory pigment in the chloroplasts of brown algae and others (like diatoms) giving them a brown or olive-green color. Like other carotenoids, it has antioxidant, anti-inflammatory, anticancer, antiangiogenic activities. Fucoxanthin suppressed the degranulation of mast cells, acting as an antiallergic. Heo and Jeon (2009) reported that fucoxanthin significantly decreased intracellular reactive oxygen species generated by exposure to ultraviolet B radiation in human fibroblast. Fucoxanthin elevated cell survival rate and inhibited cell damage for pre-treated cells, indicating that fucoxanthin could protect skin against photodamage induced by ultraviolet B irradiation from sunlight. Shimoda et al. (2010) found that fucoxanthin inhibited tyrosinase activity, melanogenesis in melanoma, and ultraviolet B-induced skin pigmentation. , Research by Urikura et al (2011) suggests that topical treatment with fucoxanthin may prevent skin photoaging and wrinkle formation in ultraviolet B-irradiated hairless mice, possibly through antioxidant and

antiangiogenic activity.

Figure. Fucoxanthin.
Heo, Soo-Jin, Jeon, You-Jin (2009) Protective effect of fucoxanthin isolated from Sargassum siliquastrum on UV-B induced cell damage. Journal of Photochemistry and Photobiology B: Biology, 95: 101-107. Shimoda H, Tanaka J, , Shan SJ, Maoka T (2010). Anti-pigmentary activity of fucoxanthin and its influence on skin mRNA expression of melanogenic molecules. J Pharm Pharmacol. 62: 1137-45. Urikura I, Sugawara T, Hirata T. (2011) Protective effect of Fucoxanthin against UVB-induced skin photoaging in hairless mice. Biosci Biotechnol Biochem. 75:757-60.

G Galangal Extract http://www.skinactives.com/Galangal-Extract.html Kaempferia galanga (lesser galangal) is a traditional aromatic plant used in tropics and subtropics of Asia for its medicinal properties and as a spice. The root extract contains chemicals with antibacterial activity, including anti-acne. It also has analgesic, anti-tumor and antiinflammatory properties, plus it smells nice! Galangal is also used as an SPF booster because it contains ethyl methoxycinnamate, a UV absorber.

Gallic acid http://www.skinactives.com/Bearberry-Extract-Uva-Ursi.html Gallic acid is a phenolic compound present in many plants, and especially abundant in the leaves of bearberry (see our bearberry extract) witch hazel (Hamamelis virginiana), the flower of mango (Mangifera indica), the fruit of emblica or amla (Phyllantus emblica), pomegranate (Punica granatum), the fuir of gall oak (Quercus infectoria), strawberry (Fragaria spp.), rhubarb (Rheum rhabarbarum) and soybean (Glycine max).

Gallic acid is a skin lightener, it inhibits tyrosinase, decreasing melanin synthesis. It is also an antioxidant that inhibits lipid peroxidation and the consequent damage to biological membranes. Gallic acid has many medicinal activities, including analgesic, antiviral, antiallergenic, antibacterial, cancer preventive, and immunomodulator.

Figure. Gallic acid Ginseng powder extract http://www.skinactives.com/Ginseng-Panax-Ginseng.html The name of this plant reflects very high expectations: the name of the genus, Panax, is derived from the Greek Panakeia, the goddess of Universal remedy), because of the miraculous virtues ascribed to it by the Chinese. Panacea was said to have a potion with which she healed the sick. This brought about the concept of the panacea in medicine, a substance meant to cure all diseases. Ginseng root contains actives like oleanolic acid, sitosterols, campesterol and more, but the actives that make it really special are the ginsenosides, higher than 80% in the standardized extract we use at Skin Actives. Ginsenosides alleviate inflammation caused by a variety of inducers, because they work by inhibiting not just one but several signaling mechanisms, including protein kinases and transcription nuclear factor-kappa B (a transcriptase) leading to a decrease in the production of cytokines and mediators of inflammation.
Lee, Davy C. W, Lau, Allan S. Y. (2011) Effects of Panax ginseng on Tumor Necrosis Factor-alphaMediated Inflammation: A Mini-Review. Molecules, 16: 2802-2816 Kim, Hei Sung, Kim, Dong Hyun, Kim, Bong Kyu, Yoon, Sungjoo Kim, Kim, Min Ho, Lee, Jun Young, Kim, Hyung Ok, Park, Young Min (2011) Effects of topically applied Korean red ginseng and its genuine constituents on atopic dermatitis-like skin lesions in NC/Nga mice. International Immunopharmacology, 11: 280-285.

Note: Ginseng extract appears in many skin care lines, like Orlane, La Prairie, 3Lab M cream, Lancme and more.

Figure. Ginseng sinensis. From Herbarium Blackwellianum emendatum Glucosamine (N-acetyl) http://www.skinactives.com/Glucosamine-N-Acetyl.html

Glucosamine, an aminosugar and one of the components of hyaluronic hcid. Hyaluronic acid (a.k.a. hyaluronan, sodium hyaluronate) is a glycosaminoglycan made of D-glucuronic acid and D-N-acetylglucosamine that make up the extracellular matrix (ground substance) of the dermis in which we also find the proteins elastin and collagen. Because of its importance, it makes sense that regular use of glucosamine in skin care may bring other benefits. These compounds bind water and are involved in the maintenance of the water and salt balance of the skin. Glusosamine has also been shown to help with several hard to treat skin problems, including atopic dermatitis and hyperpigmentation. Although the mechanism of action in unknown, it seems that glucosamine enhances the benefits of Niacinamide (whose mechanism of action on hyperpigmentation is also unknown) on hyperpigmented skin. Another nice effect of Glucosamine is through the modulation of exfoliation by keratinocytes stratum corneum. This activity is useful for people with flaky skin, a tendency to get comedos, etc. For those who have very sensitive skin or rosacea, it may help substitute for acid exfoliation (with acids like lactic, ascorbic, etc.).
Kim, C. -H., Cheong, K. A., Park, C. D., Lee, A. Y (2011) Glucosamine Improved Atopic Dermatitislike Skin Lesions in NC/Nga Mice by Inhibition of Th2 Cell Development. Scandinavian J. Immunology 73: 536-545 Callender, Valerie D., St Surin-Lord, Sharleen, Davis, Erica C., Maclin, Marissa (2011) Postinflammatory Hyperpigmentation Etiologic and Therapeutic Considerations American J. Clinical Dermatology, 87-99 Mammone T, Gan D, Fthenakis C, Marenus K (2009) The effect of N-acetyl-glucosamine on stratum corneum desquamation and water content in human skin. Journal Cosmetic Science 60 423-428 Kimball, A. B., Kaczvinsky, J. R., Li, J., Robinson, L. R., Matts, P. J.Berge, C. A.Miyamoto, K.)Bissett, D. L. (2010) Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial. British J Dermatology 162: 435-441

Figure. N-acetyl glucosamine. Glutaredoxin http://www.skinactives.com/Glutaredoxin-GRX.html

Glutaredoxin (thiol transferase) seems to provide antioxidant protection in human coronary arteries and placental function against the oxidative stress caused by preeclampsia and may even protect cerebellar granule neurons from dopamineinduced programmed cellular death. Glutaredoxin may also help catalyze the regeneration of ascorbic acid.
Starke, David W.; Chock, P. Boon; Mieyal, John J. (2003) Glutathione-Thiyl Radical Scavenging and Transferase Properties of Human Glutaredoxin (Thioltransferase). J. Biol. Chem., 278: 14607-14613. Kenchappa R.S. and Ravindranath V. (2003) Glutaredoxin is essential for maintenance of brain mitochondrial complex I: studies with MPTP. FASEB J. 17:717-719.

Figure: Schematic illustration depicting the important role of Glutaredoxin in maintaining functional integrity of mitochondrial complex I under normal conditions and during oxidative stress caused by generation of reactive oxygen species (ROS).

Glutathione (gamma-L-Glutamyl-L-cysteinyl-glycine) http://www.skinactives.com/Glutathione.html L-Glutathione (a.k.a. gamma-L-Glutamyl-L-cysteinyl-glycine) is a tripeptide composed of the amino acids L-glutamine, L-cysteine and glycine. Glutathione is a crucial element in the antioxidant defense system of the cell, together with superoxide dismutase, catalase, alpha-Dtocopherol (vitamin E), ascorbic acid (vitamin C), etc. All of these antioxidants are required to defend the cell (and the skin) from the powerful, destructive, oxidants formed during the course of metabolism, such as superoxide, hydrogen peroxide, peroxyl oxides and hydroxyl radicals. The role of glutathione is fundamental, and impairment of the glutathione system results in damage to the cell membrane and death of the cells. L-glutathione is part of the natural armamentarium our body has to protect our skin from the

reactive oxygen species that attack our skin on a continuous basis and that are largely responsible for photoaging. The problem is that there are never enough of these endogenous warriors to go around, especially not after some time in the sun. But having gluthatione around protects ascorbic acid (vitamin C), required for the synthesis of collagen and other skin constituents. For many reasons, it is a good idea to supplement endogenous glutathione with some applied topically. Glutathione, like ascorbic acid, is water soluble, a good counterpart to another antioxidant, Vitamin E, which is liposoluble. It is worth noting that the lightening activity on skin shown by hydrocoumarins and betatocopherol is through the induction of the synthesis of glutathione. It has been shown that the presence of glutathione can inhibit cell death induced by hydrogen peroxide, a powerful oxidant formed during UV irradiation. One of the effects of green tea on skin is to ameliorate to some extent the decrease in glutathione caused by UV irradiation. Glutathione is lower in photoaged and normally aged skin. Although skin ageing is clearly a multifactorial process, data indicate that the concentration of intracellular glutathione is very important and that depletion of this concentration may play a significant role in the progression of cellular ageing in human skin.
Seiji, Makota; Yoshida, Toshio; Itakura, Hideko; Irimajiri, Toshikatsu. Inhibition of melanin formation by sulfhydryl compounds. Journal of Investigative Dermatology (1969), 52(3), 280-6. Kohn, Robert R. (1955) Glutathione inhibition of melanin synthesis in vitro. Enzymologia, 17: 1938.

Figure. Glutathione Glycan booster http://www.skinactives.com/Glycan-7-Booster.html Our Glycan-7 booster blend is a combination of plant and fungal extracts that will promote collagen synthesis and fibroblast division and modulate the immune response. This mix includes glycans from aloe, apple, larch, yeast, oat, and brown algae. This group of seven is just a selection from the many glycans we offer that benefit the skin.

Aloe Vera (http://www.skinactives.com/Aloe-Extract.html)- The gel obtained from Aloe

barbadensis plant improves skin hydration, has anti-inflammatory properties and aids healing of cuts, grazes, burns and insect bites. The polysaccharides in this extract include acetylated mannans. Apple pectin is a complex polysaccharide that contains rhamnose. Fibroblasts contain receptors for rhamnose (more about this later), and binding of rhamnose to the receptor leads to increased synthesis of collagen and strengthened epidermal-dermal junction. Apple pectin helps thicken skin thinned by aging. Larch arabinogalactans (http://www.skinactives.com/Larch-Arabinogalactans.html) - In native North American Indian tribes, larch was used as a poultice on sores, ulcers, burns and to alleviate itching. When biochemists looked into larch, they found that arabinogalactans stimulate dermal fibroblast activity and proliferation, promote keratinocyte differentiation and the production of keratinocyte growth factor. Note: Dr. Andrew Weil, a proponent of integrative medicine (which incorporates scientifically proven botanicals into the daily practice of medicine) uses this active in his Origins line. Yeast beta glucan (http://www.skinactives.com/Beta-Glucan-Yeast.html) - The cell wall of yeast is very complex, with a structure that includes beta(1--> 3)-glucan, beta(1--> 6)-glucan, chitin, and mannoprotein. When we come in contact with these special glycans, our immune system is activated so that, when a pathogen is encountered, we are better able to deal with it and stop an infection. Apparently, this response may also prepare us to stop our own "gone bad" cells, those that have lost the capacity to control cell division and have become cancer cells. A great advantage to allergy sufferers: yeast beta glucan (and that of other fungi) seems to decrease the tendency to allergic responses and inflammation, and as an added bonus it tightens your skin. A recently discovered lectin is dectin-1, a small cell surface protein that recognizes beta 1,3 and beta1,6-glucans and is a source of innate immunity, in other words it does not require previous exposure to pathogen. Fucoidan (http://www.skinactives.com/Fucoidan-Brown-Alga-Phaeophyta.html)- Fucoidans are sulfated polysaccharides that when applied to the skin increase the density of collagen bundles, decrease activity of proteases (enzymes that break down dermal proteins), increase scavenging of free radicals, and increase cell proliferation. In addition to helping with healing and collagen synthesis, fucoidan inhibits the replication of many viruses, including herpes, human cytomegalovirus, and HIV-1. Prickly pear (Opuntia fruit) extract - This beautiful fruit contains methylated rhamnogalacturonans (L-arabinose and D-xylose are also represented), giving this extract

medicinal powers in treatment of burns, edema, and asthma. Beta glucan (oat) (http://www.skinactives.com/Beta-Glucan-from-Oat.html) - Cereal beta-glucan is a mix of linked (1 -> 3) (1 -> 4)-beta-D-glucan with anti-inflammatory properties.

Granulysin http://www.skinactives.com/Granulysin.html This new anti-acne active developed by Skin Actives for use in skin care is a member of lysosomal proteins (saposins-like) that function as activator of various lysosomal lipid-degrading enzymes. Granulysin is expressed by activated human killer cells and T-lymphocytes and it exhibits activity against Gram-positive and Gram-negative bacteria and fungi. One of the advantages of this particular protein is that it will help keep at bay the acne bacteria, Propionibacterium acnes. It works by creating holes in the target cell membrane.

Figure: Schematic diagrams of granulysin action. (a) Ellipses represent Granulysin molecules, with a cluster of positive charges (+++), and more positive charges distributed elsewhere. The

charge cluster of the Granulysin molecule in solution (1) orients the molecule (2) towards the negatively charged surface of the bacterial cell (line with dashes). The arginine residues bind surface charges (3). The Granulysin molecules could cluster at the cell surface (4). Granulysin lyses the membrane (5), possibly rolling the granulysin in the direction of the lytic surfaces of helices 1, 2, and 3. (b) The lysis process could involve a scissors motion enabled by the internal voids further exposing lytic surface.
Bleackley, R. C., Lobe, C. G., Duggan, B., Ehrman, N., Fregeau, C., Meier, M., Letellier, M., Havele, C., Shaw, J., Paetkau, V. (1988) The isolation and characterization of a family of serine protease genes expressed in activated cytotoxic T lymphocytes Immunol. Rev. 103,519. Jenne, D. E., Masson, D., Zimmer, M., Haefliger, JA., Li, WH., Tschopp, J. (1989) Isolation and complete structure of the lymphocyte serine protease granzyme G, a novel member of the granzyme multigene family in murine cytolytic T lymphocytes. Evolutionary origin of lymphocyte proteases Biochemistry 28,79537961. Jenne, D. E., Tschopp, J. (1988) Granzymes, a family of serine proteases released from granules of cytolytic T lymphocytes upon T cell receptor stimulation Immunol. Rev. 103,5371. Jongstra, J., T J Schall, B J Dyer, C Clayberger, J Jorgensen, M M Davis, A M Krensky (1987) The isolation and equence of a novel gene from a human functional T cell line. J. Exp. Med . 165:601614.

Grape (Vitis vinifera) seed extract. http://www.skinactives.com/Grape-Seed-Proanthocyanidins.html Grape seed extract is a source of proanthocyanidins, flavonoids that protect capillary walls and inhibit the enzymes that break down collagen (collagenase), hyaluronic acid (hyaluronidase) and elastin (elastase). Also anti-inflammatory, antihistamines, antiallergenic, and as major free radical scavengers. Proanthocyanidins also help promote tissue elasticity, help heal injuries, reduce swelling and edema, restore collagen and improve peripheral circulation. Proanthocyanidins also prevent bruising, strengthen weak blood vessels and reduce histamine production. Note: See also pine proanthocyanidins.
Garbacki, N.; Kinet, M.; Nusgens, B.; Desmecht, D.; Damas, J.(2005) Proanthocyanidins from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1. Journal of Inflammation (London, United Kingdom) 2:9 Blazs, G. Gbor, M. "Oedema-inhibiting effect of procyanidin." Acta Physiologica Academiae Scientiarum Hungaricae, Tomus (1980). 56(2) pp. 235-240. Bouhamidi R, Prevost V, Nouvelot A. (1988) High protection by grape seed proanthocyanidins (GSPC) of polyunsaturated fatty acids against UV-C induced peroxidation. C R Acad Sci III, 321(1):31-8. Fitzpatrick DF, Bing B, Rohdewald P. (1998) Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol., 32(4):509-15. Packer L, Rimbach G, Virgili F. (1999) Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med., 27(5-6):704-24.

Figure. Epicatechin, one of the building blocks of proanthocyanidins.

H Hesperidin http://www.skinactives.com/Hesperidin.html This flavonoid is present in lemons and oranges and has antioxidant and anti-inflammatory activity and reduces capillary permeability used to be called vitamin P but it is not a vitamin. It also anti-allergic, vasoprotective and cancer preventive activities and may stimulate mitochondrial activity.
Iwai, I.; Yamashita, T.; Ochiai, N.; Masuda, Y.; Hosokawa, K.; Kohno, Y. (2003) Development of skincare lipsticks on the basis of dermatological study of lips Nippon Koshohin Kagakkaishi, 27(2), 7985. Kubo, M.; Fujita, T.; Nishimura, S.; Tokunaga, M.; Matsuda, H.; Gato, T.; Tomohiro, N.; Sasaki, K.; Utsunomiya, N. (2004) Seasonal variation in anti-allergic activity of Citrus fruits and flavanone glycoside content. Natural Medicines (Tokyo, Japan), 58(6), 284-294. Yoshioka, K.; Murayama, S.; Kaneyoshi, J.; Furuya, H.; Yoshimitsu, K.; Sakanaka, S.; Miwa, N. (2003) Synergistic effects of vitamins P (Hesperidin) and C of health food on skin rejuvenation. Bio Industry, 20(5), 19-29

Figure. Hesperidin.

Hesperidin methyl chalcone Present in Ruscus and other plants, this active is used in the treatment of venous insufficiency.
Bouskela, Eliete; Cyrino, Fatima Z. G. A.; Marcelon, Gilbert (1993) Inhibitory effect of the Ruscus extract and of the flavonoid hesperidin methylchalcone on increased microvascular permeability induced by various agents in the hamster cheek pouch. J. Cardiovascular Pharmacology, 22: 225-30.

Horse Chestnut (Aesculus hippocastanum ) Extract and Escin (aescin) http://www.skinactives.com/Horse-Chestnut.html Aescin is not a single chemical but a family of compounds, glycosides of saponins present in horse chestnut (Aesculus hippocastanum) extract. They have strong anti-inflammatory and antioxidant effects. Through their action on connective tissue, they strengthen fragile capilliary blood vessels, thus helping to prevent leakage of fluids into surrounding tissues and decreasing exudation and edema development. Horse chestnut extract has other valuable chemicals, including the antioxidants quercetin and kaempferol but, because of the special properties of escin, at Skin Actives we use an extract standardized (i.e. enriched so that it has a very high minimal concentration) for this particular chemical. Aescin is believed to foster healthy tone in vein walls by inhibiting enzymes that attack the interior of the veins, it also facilitates the contraction of elastic fibers in blood vessel walls, thereby elevating the flexibility of the vessels. This extract is used topically to help with varicose veins, swelling, and oxidative stress. Rutin, another chemical present in Horse Chestnut extract, also strengthens fragile capillaries, working synergistically with escin to promote vascular health. Aescin inhibits elastase and hyaluronidase, preserving the structure and volume of the dermis matrix.
Vogel, Guenther; Marek, Marie L.; Oertner, Roswitha (1970) Mechanisms of therapeutic and toxic actions of the horse chestnut saponin escin. Arzneimittel-Forschung: 20(5), 699-703. Magliulo, E.; Carco, F. P.; Gorini, S.; Barigazzi, G. M (1968) In vivo and in vitro studies on the antiinflammatory action of the escin. Archivio per le Scienze Mediche (1968), 125(6), 207-18. Suter, Andy; Bommer, Silvia; Rechner, Jordan (2006) Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies. Advances in Therapy: 23(1), 179-190. Guillaume, M.; Padioleau, F (1994) Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract. Arzneimittel-Forschung, 44(1): 25-35. Berti, Ferruccio; Omini, Claudio; Longiave, Daniela (1977) The mode of action of escin and the release of prostaglandins. Prostaglandins, 14(2): 241-9.

Horsetail powder http://www.skinactives.com/horsetail-powder.html Equisetum (horsetail, scouring rush) is a very primitive vascular plant. Horsetail (Equisetum hyemale) powder is used as exfoliator, it will make your skin feel cleaner and smoother. Horsetail Powder contains silicic acid (promotes collagen synthesis), ferulic acid (anti-cancer, analgesic, anti-allergic) and caffeic acid (antiseptic).

Figure. Equisetum (horsetail). Hyaluronic acid http://www.skinactives.com/Hyaluronic-Acid.html Hyaluronic acid (a.k.a. hyaluronan, sodium hyaluronate) is a polysaccharide, made by animals and some bacteria, with long chains made of N-acetyl-D-glucosamine alternating with glucuronic acid. In our skins, it stabilizes the intercellular (in-between cells) space in the dermis, and contributes significantly to cell proliferation, migration, and skin repair, activities essential to skin health. By definition, the molecular weight of hyaluronic acid is in the millions. Small fragments of broken hyaluronic acid cant hold water or form gels. Because of its tremendous capacity to hold water, adding this active to your creams, lotions, gels

or serums will help keep skin moist. Also, hyaluronidase in the skin will break this active down and the sugars released will be used to make new Hyaluronic Acid in our dermis.

Figure. Structure of Hyaluronic acid. The n indicates that the subunit (glucuronic acid at left, glucosamine at right) between brackets is repeated thousands of time to form the very large polymer.

Hydroquinone. Note: not sold or used by SAS This chemical inhibits the synthesis of melanin by inhibiting one of the enzymes in the synthetic pathway, and it also kills the melanocites that make it. Among its possible side effects after longterm use: exogenous ochronosis, i.e. hyperpigmentation accompanied by degeneration of collagen and elastin. Hydroquinone also irritates the skin and it has been blamed for the carcinogenic effects of tobacco smoking. Healthier options include: kojic acid (we use the dipalmitate), azelaic (we use azeloyl glycine) and betulinic acid, licorice extract and others, in conjunction with other ingredients. These ingredients may take longer to give visible results but maybe we should remember that melanin takes time to accumulate so it will take time and new cells for the skin to get lighter.

Figure. Hydroquinone. I Idebenone http://www.skinactives.com/Idebenone.html Chemical name 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-cyclohexa-2,5-diene-1,4-dione. This analog of Coenzyme Q10 is not just an antioxidant but it can help with mitochondrial

function and, therefore, with energy production by the skin cells. This synthetic chemical was developed to help with mitochondrial disfunction in the brain (exogenous CoQ10) will not pass the blood-brain barrier). Because mitochondria age faster than the rest of the cells, idebenone is advertised as anti-aging. Warning: some idebenone users may develop a persistent allergy to this synthetic chemical.

Figure. Idebenone J Jiaogulan (Gynostemma pentaphyllum) extract http://www.skinactives.com/Jiaogulan-Extract-Gynostemma-pentaphyllum.html As a tea, jiaogulan "benefits Qi, enriches the blood, keeps the heart in good shape, and relieves uneasiness of body and mind". In Chinese, xiancao, literally "immortal grass"; more accurately "herb of the inmortals") For those who want scientific information rather than Qi: Jiaogulan extract can absorb UV (increasing the SPF of any sunblock), and gypenosides can protect vascular endothelial cells from oxidant injury. A polysaccharide in Jiaogulan may decrease tumor necrosis factor-alpha (TNF-alpha), a key pro-inflammatory cytokine in psoriasis. Jiaogulan extract modulates immune activity probably through increased activities of macrophages, T lymphocytes and natural killer cells.
Aktan, Fugen; Henness, Sheridan; Roufogalis, Basil D.; Ammit, Alaina J (2003) Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF- B-mediated iNOS protein expression. Nitric Oxide, 8: 235-242. Li L; Jiao L; Lau B H (1993) Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes. Cancer biotherapy 8: 263-72. Li, Lin; Lau, Benjamin H. S. (1993) Protection of vascular endothelial cells from hydrogen peroxideinduced oxidant injury by gypenosides, saponins of Gynostemma pentaphyllum. Phytotherapy Research, 7: 299-304. Li, Xiao-Li, (Wang, Zheng-Hui, Zhao, Yong-Xi, Luo, Su-Ju, Zhang, Ding-Wei, Xiao, Sheng-Xiang, Peng, Zhen-Hui (2012) Purification of a polysaccharide from Gynostemma pentaphyllum Makino and its therapeutic advantages for psoriasis. Carbohydrate Polymers, 89: 1232-1237

Figure. Jiaogulan leaves Jojoba (Simmondsia chinensis) oil

Jojoba is a shrub a native to the Mojave and Sonoran deserts of Arizona, California and Mexico. Jojoba

seed contains a light-gold colored liquid wax ester which is the primary storage lipid of the plant. Conventional oilseed crops, such as soybean, corn, olive, or peanut produce oils (and not wax esters) as the primary storage lipid. Jojoba wax (called oil) makes up 50% of the seed's dry weight. Since it is composed of wax esters, it is an extremely stable substance and does not deteriorate easily. Jojoba oil is absorbed quickly and is excellent for dry and mature skins, especially when the skin is inflamed. In most cases it can be used on acne skin without any problems as it helps to control acne.

Figure. A jojoba shrub in Arizona.

Go to top K Keratinocyte Growth Factor (KGF) http://www.skinactives.com/Keratinocyte-Growth-Factor-BT-KGF.html This growth factor has been proven to stimulate hair growth in laboratory studies. It also accelerates healing and increases skin volume. It may also help prevent hair loss during radiation therapy during cancer treatment. Keratinocyte Growth Factor (KGF) binds to the KGF receptor on the cell surface, acting as both a growth and survival factor by stimulating epithelial cell proliferation, differentiation, and migration and promoting a number of cell protective mechanisms. KGF is also known as FGF-7 and heparin-binding growth factor-7 (HBGF-7). KGF is a member of the fibroblast growth factor family and has been found to stimulate hair growth. Cells that respond to KGF do so because they have receptors on the cell membrane that recognize the growth factor, normally produced by cells near or far from the target cell. The binding of the Growth Factor to the receptor initiates a cascade of molecular events that will eventually lead, among other effects, to cell division. Keratinocyte growth factor has been shown to regulate proliferation and differentiation in epithelial tissues and may regulate the stem cells of the hair follicle.

(ReVive has also used KGF in a volumizing serum which they sell for $600 per unce.)

Jang, JH (2005) Stimulation of human hair growth by the recombinant human keratinocyte growth factor-2 (KGF-2). Biotechnology Letters, 27:749-52. Guo, Lifei; Degenstein, Linda; Fuchs, Elaine (1996) Keratinocyte growth factor is required for hair development but not for wound healing. Genes & Development 10:165-75. Beer, HD, Bittner, M, Niklaus, G, Munding, C, Max, N); Goppelt, A, Werner, S (2005) The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair. ONCOGENE, 24: 5269-5277 Karvinen, S; Pasonen-Seppanen, S; Hyttinen, JMT; Pienimaki, JP; Torronen, K, Jokela, TA; Tammi, MI, Tammi, R (2003) Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthases 2 and 3. J Biol Chem, 278:49495-49504 Braun, Susanne, Krampert, Monika, Bodo, Enikoe, Kuemin, Angelika, Born-Berclaz, Christiane, Paus, Ralf, Werner, Sabine. (2006) Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents Journal Cell Science, 119: 48414849 Danilenko, Dimitry M.; Ring, Brian D.; Yanagihara, Donna; Benson, William; Wiemann, Bernadette; Starnes, Charles O.; Pierce, Glenn F. (1995) Keratinocyte growth factor is an important endogenous mediator of hair follicle growth , development, and differentiation. Normalization of the nu/nu follicular differentiation defect and amelioration of chemotherapy induced alopecia. American Journal of Pathology 147: 145-54.

Kinetin http://www.skinactives.com/Kinetin-10.html Kinetin is a derivative of adenine, one of the nucleic acid bases that form DNA and RNA. A plant growth hormone, kinetin appears to be a beneficial anti-oxidant applied topically to the skin. We recommend use of our coconut endosperm over the use of kinetin, as coconut endosperm contains all the beneficial chemicals in Kinetin as well as many others that work in synergy. The cytokinins (plant growth factors that regulate various aspects of plant growth and differentiation.) kinetin and zeatin have been shown to have growth-modulating, antioxidative and antisenescence effects in human skin cells. Kinetin application also stimulated the formation of elastin and fibrillin-1 deposition in the upper dermis and stimulated their perpendicular organization to the dermoepidermal junction. Note: This is the active ingredient in the Kinerase range of products.

Figure. Kinetin
Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea Wu, J. J, Weinstein, G. D.; Kricorian, G. J.; Kormeili, T.; McCullough, J. L. (2007) Clinical & Experimental Dermatology, 6: 693695. Rattan SI, Clark BF. (1994) Kinetin delays the onset of ageing characteristics in human fibroblasts. Biochem Biophys Res Commun 201: 66572. Sharma SP, Kaur P, Rattan SI. Plant growth hormone kinetin delays ageing, prolongs the lifespan and slows down development of the fruitfly Zaprionus paravittiger. Biochem Biophys Res Commun 1995; 216: 106771. Hsiao G, Shen M, Lin K et al. Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo. Eur J Pharmacol 2003; 465: 2817. McCullough JL, Weinstein GD. Clinical study of safety and efficacy of using topical kinetin 0.10% (Kinerase) to treat photodamaged skin. Cosmetic Dermatol 2002; 15: 2932. Draelos ZD. Clinical situations conducive to proactive barrier enhancement. Cutis 2002; 70: 1720. Elewski BE, Fleischer AB Jr, Pariser DM. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial . Arch Dermatol 2004; 139: 144450. Van Staden J, Cook EL, Nooden LD. Cytokinins and senescence. In: Senescence and Aging in Plants (NoodenLD, LeopoldAC, eds). New York: Academic Press, 1988; 281328. Rattan SI, Sodagm L. Gerontomodulatory and youth-preserving effects of zeatin on human skin fibroblasts undergoing aging in vitro. Rejuvenation Res 2002; 8: 4657. Vicanova J, Bouez C, Lacroix S et al. Epidermal and dermal characteristics in skin equivalent after systemic and topical application of skin care ingredients. Ann N Y Acad Sci 2006; 1067: 33742.

Kojic acid dipalmitate http://www.skinactives.com/Kojic-Acid-Dipalmitate.html Kojic acid is used in cosmetics for its excellent whitening effects. Kojic acid dipalmitate is a derivative of kojic acid and a fatty acid (palmitic acid), this chemical modification makes it more stable and oil soluble. Chemical names often have an historic root; at the beginning of the XXth century kojic acid was isolated from "koji" (malted rice). Nowadays, kojic acid is produced by

fermentation of carbohydrate by Aspergillus oryzae. Kojic Acid is known for its nonproblematic biodegradation, and is used in Japan in a variety of food and drink preparation methods. Other useful properties of kojic acid are its antifungal abilities and its capacity to chelating heavy metals.

O O O Me (CH 2 ) 14 C O O CH 2 O C (CH 2 ) 14 Me

Note: Brands that use kojic acid dipalmitate include Jan Marini Age Intervention; Dermaquest Skin Therapy Skin Vitalight; Blanc Expert line.
Note: Cosmelan 2 Maintenance depigmenting cream uses kojic acid (not modified), more unstable and irritating to the skin.

Larch arabinogalactans
http://www.skinactives.com/Larch-Arabinogalactans.html

In European folklore the larch tree was believed to prevent enchantment; the smoke from burning larch bark was thought to drive away evil spirits, and parents had children wore collars of larch bark as a protection against the evil eye. In native North American Indian tribes, larch was used as a poultice on sores, ulcers, burns and to alleviate itching. When biochemists looked into larch, it was found that arabinogalactans stimulate dermal fibroblast activity and proliferation, explaining the traditional use of larch bark for wound healing. Larch arabinogalactans promote keratinocyte differentiation and the production of keratinocyte growth factor. Our extract is standardized for arabinogalactans but it likely contains some betulin, a great active (please read about betulinic acid in our website).

Figure: Tamarack larch, American larch, Larix laricina. Zippel, Janina, Deters, Alexandra, Hensel, Andreas (2009) Arabinogalactans from Mimosa tenuiflora (Willd.) Poiret bark as active principles for wound-healing properties: Specific enhancement of dermal fibroblast activity and minor influence on HaCaT keratinocytes. J Ethnopharmacology 124: 391-396

Note: Dr. Andrew Weil, a proponent of integrative medicine (which incorporates scientifically proven botanicals into the daily practice of medicine) uses this active in his Origins line.

Lecithin http://www.skinactives.com/Lecithin.html Skin Actives lecithin is extracted from non-GMO soy. Lecithin is a mixture of polar and nonpolar lipids with a polar lipid content of at least 50%. The most important chemical in lecithin is phosphatidylcholine, but other lipids in lecithin are also important constituents of the cell membrane systems, crucial to keep the cell intact and functional.

Figure. Lecithin.

Liquid crystal http://www.skinactives.com/Liquid-Crystal.html A mix of cholesterol derivatives that will replenish membrane lipids. Very emollient and with very special optical properties. Ingredients: Cholesteryl Oleyl Carbonate, Cholesteryl Nonanoate, Cholesteryl Chloride, antioxidant.

Liquorice (Glycyrrhiza glabra) root extract http://www.skinactives.com/Licorice-Extract.html Licorice root has been used in Europe since prehistoric times, documented since the ancient Greeks, for its anti-inflammatory and antimicrobial activity. Phytochemists and biochemists have been working for decades elucidating the structure of the chemicals involved and mechanisms of action. In the case of the root of Glycyrrhiza glabra this is not a single chemical that benefits the skin, but rather a combination of many chemicals. From all the active chemicals in licorice (Glycyrrhiza glabra) root extract, glabridrin is the one most responsible for the beneficial effect of licorice on the skin. Glabridrin inhibits the activities of two tyrosinase isozymes, T1 and T3 (and melanin synthesis) without affecting cell proliferation. Topical application of glabidrin prevented pigmentation and erythema induced by UV-B. The anti-inflammatory effect of this chemical is through the inhibition of superoxide anion production and cyclooxygenase activity. For all of these reasons, glabridrin is a good inhibitor of melanogenesis and skin inflammation.
Hwang, Jung-Hee; Lee, Byung Mu. (2007) Inhibitory effects of plant extracts on tyrosinase, L-DOPA oxidation, and melanin synthesis. Journal of Toxicology and Environmental Health, Part A, 70(5), 393407. Kim, Hyoung Ja; Seo, Seon Hee; Lee, Byeong-gon; Lee, Yong Sup Identification of tyrosinase inhibitors from Glycyrrhiza uralensis. Planta Medica (2005), 71: 785-787.

Note: Products that contain liquorice are Shiseido UV White Control and Protect Base, Shiseido White Lucency Concentrated Brightening Facial Serum, Cosme Decorte Whiteologist Sports Concentrate, Vichy Bi-White Reveal Double Corrective Whitening Essence, la prairie Cellular Intensive Anti-Wrinkle AntiSpot Cream

Lutein http://www.skinactives.com/Lutein-Concentrate.html Lutein is used by our body but we humans cannot make it, so we need to obtain it from food or apply it topically. Although its main role seems to be vision (in the lens and macula lutea of the eye), lutein may also provide protection against UV -induced redness, inflammation, and wrinkling. It also helps maintain skin hydration, smoothness and elasticity.

Figure: Lutein Luteolin Luteolin is a flavonoid, it is one of the more common flavones. It is an antioxidant and a scavenger of free radicals. It also suppresses activation of metalloproteinases by UV light, a possible mechansim for prevention of photoaging.

Figure: Luteolin.
Lim, Sung H.; Jung, Sung K.; Byun, Sanguine; et al. (2013) Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90RSK2. Journal Cellular Molecular Medicine. 17: 672-680. Woelfle, Ute; Esser, Philipp R.; Simon-Haarhaus, Birgit; et al.(2011)UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo. Free radical Biology and Medicine, 50: 1081-1093

Lycopene http://www.skinactives.com/Lycopene-Concentrate.html This carotenoid is the antioxidant heart of tomato, Lycopersicon esculentum, and responsible for the many health benefits of tomato (tomato eaters have lower risk of several types of cancer). If you want to give your cream, lip treatment, or mineral make up a red color this is the perfect active. Lycopene is responsible for many of the health benefits of tomato. Tomato eaters have lower risk of several types of cancer. Lycopene traps singlet oxygen, making it a great antioxidant. At physiological concentrations it inhibits cell growth of some human cancers without toxic effects on normal cells, apparently by upregulating a gene, connexin 43, that restores cells to normal proliferation. The combination of Lycopene and Lutein synergistically interact as antioxidants, and this may relate to specific positioning of different carotenoids in membranes. An optimal supply of antioxidants like lycopene to the skin increases skin defense against UV irradiation, supports longer-term protection, and contributes to maintenance of skin health and appearance.

Figure. Lycopene M Macrocystis pyrifera Macrocystis pyrifera, the substrate in our bioferment, is a brown algae (Phaeophyta) and a rich source of iodine, potassium and many essential minerals. It also contains organic chemicals like alginic acid, fucoidans, laminaran, laminitol, lutein, zeaxanthin, xanthophyll, violaxanthin, fucosterol, sulpholipids, inositol, phytol, phloroglucinol, aldobiuronic acid and much more.

Figure. Macrocystis pyrifera Magnesium ascorbyl phosphate http://www.skinactives.com/Magnesium-Ascorbyl-Phosphate-MAP-Vitamin-C.html Magnesium ascorbyl phosphate (MAP) is a stable form of Vitamin C, a vitamin necessary to synthesize collagen in the step of hydroxylation of amino acid proline. Scurvy, a syndrome of vitamin C deficiency, is related to defective collagen synthesis.
OH O O R OH

S H

HO

OH

Properties: skin lightener. Once MAP is applied to the skin it will be transformed by enzymes into ascorbic acid, an antioxidant and a cofactor for an enzyme crucial in the synthesis of collagen (prolyl hydrolase). As an antioxidant agent, vitamin C scavenges and destroys reactive oxidizing agents and other free radicals. Because of this ability, it provides important protection against damage induced by UV radiation (and the DNA mutations and cancer that may result from it). Vitamin C also improves skin elasticity, decreases wrinkles by stimulating collagen synthesis, reduces erythema, promotes wound healing. Because body control mechanisms limit the amount of ingested vitamin C available to skin, topical antioxidant therapy becomes an efficient way to target the vitamin directly.

Takashima, Hiromichi; Nomura, Hiroaki; Imai, Yoshio; Mima, Hiroyuki (1971) Ascorbic acid esters and skin pigmentation. American Perfumer and Cosmetics, 86: 29-36. Products that contain magnesium ascorbyl phosphate: Shiseido UV White Control and Protect Base, Shiseido Revital Cream, ULTIMA II Vital Radiance Skin Renewing Toner, ~H2O+ Plus Waterwhite Brightening Tonic, La Prairie Cellular Intensive Anti-Wrinkle Anti-Spot Cream

Mangosteen (Garcinia mangostana) http://www.skinactives.com/Mangosteen-Extract-Garcinia-Mangostana.html Mangostin and other xanthone derivatives are the chemicals in mangosteen that may be responsible for its anti-inflammatory activity. The mechanism of action is through inhibition of histamine release, and inhibition of cyclooxygenase and prostaglandin E2 synthesis. Gammamangostin and rubraxanthone have shown to lead some cancer cell types to apoptosis (cell death).

Figure. Purple mangosteen. From: Garcinia mangostana L. from "Fleurs, Fruits et Feuillages Choisis de l'Ile de Java" [Selected Flowers, Fruit and Foliage from the Island of Java] by Berthe Hoola van Nooten (1817-1892), Pieter De Pannemaeker (lithographer)

Figure. Mangostin Melatonin http://www.skinactives.com/Melatonin.html Secreted by the pineal gland in response to sunlight, it has been shown to decrease accumulation of melanin. Topical use of synthetic melatonin appears to be beneficial to the skin in many ways. Used in conjunction with magnesium ascorbyl phosphate (MAP), melatonin improves skin elasticity. It may also help with mouth sores (stomatitis), decrease the effect of radiotherapy on the skin and improve skin texture. Melatonin may help improve hair texture in female alopecia.

Figure: Melatonin N-[2-(5-methoxy-1H-indol-3-yl)ethyl] acetamide

Slominski, Andrzej; Fischer, Tobias W.; Zmijewski, Michal A.; Wortsman, Jacobo; Semak, Igor; Zbytek, Blazej; Slominski, Radomir M.; Tobin, Desmond J. (2005) On the role of melatonin in skin physiology and pathology. Endocrine: 27:137-147. Varvaresou, Athanasia; Tsaoula, Eleana; Tsirivas, Efthimios (2003) The influence of the addition of melatonin to a magnesium ascorbyl phosphate-containing formulation on the mechanical properties of human skin. Epitheorese Klinikes Farmakologias kai Farmakokinetikes, International Edition :17:177181. Bangha E, Elsner P, Kistler GS (1997) Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point. Dermatology,195: 248-52.

Menthol and related compounds We don't sell or use menthol in SAS products. Why is menthol here? It is an irritant, but it is widely used in skin and hair care because it gives people the illusion that something must be working.

Figure. Menthol. Methionine Sulfoxide Reductase (MSR)

http://www.skinactives.com/Methionine-Sulfoxide-Reductase-MSR.html MSR repairs protein damage caused by reactive oxygen species that escaped the first line of antioxidant defense. In the scalp, MSR can fix oxidized amino acids (methionine) in a damaged tyrosinase protein so that the enzyme can keep catalyzing the first key step in the synthesis of melanin. The crucial role of MSR is not limited to the scalp. Oxidation of proteins by reactive oxygen species is associated with aging, oxidative stress, and many diseases. Protein-bound methionine residues are among the most susceptible to oxidation by reactive oxygen species (ROS), resulting in formation of methionine sulfoxide residues Met(O), but this deleterious modification can be repaired by methionine sulfoxide reductase which catalyzes the thioredoxindependent reduction of free and protein-bound Met(O) to methionine
Moskovitz, J., Bar-Noy, S., Williams, M. W., Requena, J., Berlett, S. B. & Stadtman, E. R. (2001) Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals, Proc. Natl. Acad. Sci. USA 98 , 12920-12925. Wood, J. M., Decker, H., Hartmann, H., Chavan, B., Rokos, H., Spencer, J. D., Hasse, S. Thornton, M. J., Shalbaf, M., Paus, R., Schallreuter, K. U. (2009) Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methioninesulfoxide repair. FASEB Journal, 23(7):2065-75.

Mitochondria Concentrate http://www.skinactives.com/Mitochondria-Concentrate.html Mitochondria (sing. mitochondrion, from the Greek mitos, warp thread + Greek khondrion, diminutive of khondros, grain, granule). Mitochondria provide the energy as adenosine triphosphate (ATP), the form of energy our cells can use to do housekeeping, grow and divide. This is true not just for us, humans, but for all eukaryotes (organisms with nuclei). Mitochondria use molecular oxygen to extract a lot of energy that would otherwise be lost, and foodstuff is eventually converted to low energy water and carbon dioxide. This great energy-converting efficiency comes at a cost: mitochondria produce strong oxidants like hydrogen peroxide and the superoxide and hydroxyl radicals as by-products. All of the cell sophisticated antioxidant mechanisms (including vitamin C, glutathione and vitamin E) cant completely protect mitochondria from slow but persistent damage. This oxidative stress makes mitochondria age at a faster pace than the rest of the cell, because oxidation of lipids, proteins, RNA, and DNA is faster. Indeed, oxidative damage to mitochondrial DNA (the only organelle with its own DNA outside the nucleus) is 8 to 10-fold higher than the damage found in nuclear DNA. Oxidative damage also affects adversely the inner mitochondrial membrane, where the crucial enzyme ATPase is located and where ATP is produced. The phospholipids of the inner mitochondrial membrane change and become even more sensitive to oxidative damage. These

changes are bound to affect membrane fluidity and permeability and will certainly impair the ability of mitochondria to meet cellular energy demands. This oxidant-induced acceleration of senescence has major consequences for mitochondria: aging mitochondria lose efficiency in their job of extracting the last bit of energy from foodstuff: enzyme activity and substrate binding affinity decrease. This decay in function can be partially reversed in aged animals by feeding them the mitochondrial metabolites acetyl carnitine and lipoic acid, and information of this sort provides circumstantial evidence for the mitochondrial theory of aging (a.k.a. free radical theory of aging) which states that the slow accumulation of impaired mitochondria is the driving force of the aging process. Even if we dont accept the theory that mitochondrial aging is the cause of overall aging, there is no doubt that deterioration of mitochondria is at least responsible for the aging of the whole organism. Up to now, this information has been translated into the topical application of alpha lipoic acid, acetyl carnitine and various antioxidants in anti-age skin care products. We isolate the mitochondrial fraction from fresh cauliflower florets using proprietary methods. The fraction is shipped as a concentrate in a glycerol/water solution containing reduced glutathione and preservative.
Harman, D. (1983). Free radical theory of aging: consequences of mitochondrial aging. Age 6:8694. Hampton, T. (2005) Study reveals mitochondrial role in aging. JAMA, 294:672. Ma, Yi-Shing, Wu, Shi-Bei, Lee, Wan-Yu, Cheng, Ju-San, Wei, Yau-Huei (2009) Response to the increase of oxidative stress and mutation of mitochondrial DNA in Aging. Biochim. Biophys. Acta General 1790 1021-1029. Birch-Machin, MA., Swalwell, H (2010) How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue Mutagenesis 25:101-107. Larsson, Nils-Goeran (2010) Somatic Mitochondrial DNA Mutations in Mammalian Aging. Annual Review of Biochemistry 79: 683-706 Koziel, Rafal, Greussing, Ruth, Maier, Andrea B., Declercq, Lieve, Jansen-Duerr, Pidder (2011) . From Functional Interplay between Mitochondrial and Proteasome Activity in Skin Aging J. Investigative Dermatology, 131: 594-603

See also http://en.wikipedia.org/wiki/Mitochondria

Figure. Mitochondrion (diagram) Myricetin from Bayberry (Myrica rubra) bark http://www.skinactives.com/Myricetin-Bayberry-Bark-Extract.html Our bayberry bark powder extract is standardized for myricetin (>80%). Myricetin seems to decrease two effects of UV radiation: thickening of skin and wrinkle formation, and increased activity of matrix metalloproteinase. Myricetin also quenches noxious hydrogen peroxide and prevents lipid peroxidation.
Jung, Sung Keun, Lee, Ki Won, Kim, Ho Young, Oh, Mi Hyun, Byun, Sanguine, Lim, Sung Hwan, Heo, Yong-Seok, Kang, Nam Joo, Bode, Ann M., Dong, Zig, Lee, Hyong Joo. (2010) Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf. Biochemical Phramacology, 79: 1455-1461. Huang, Jheng-Hua, Huang, Chieh-Chen, Fang, Jia-You, Yang, Cheng, Chan, Chi-Ming, Wu, Nan-Lin, Kang, Shung-Wen, Hung, Chi-Feng (2010) Protective effects of myricetin against ultraviolet-B-induced damage in human keratinocytes . Toxicology in vitro, 24:21-28.

Figure. Myricetin. Natto gum A.k.a. (poly gamma glutamate, gamma PGA), is an excellent moisturizer, improves the texture of skin and hair and it seems to enhance the immune system. The industry likes to call it phytocollagen, a very bad name because plants dont have collagen (or elastin, for that matter).
Note: natto gum is used in brand names Chantecaille, DHC, Shiseido , Estitica Emilia, Hypanique, Isoral, Natural Cycle, Noevir, Oguma, Oripan, Phyto, Saniforma, Shoei, Shu Uemura, Skin Lux, Topo, Utako, Youngblood, Dermaplus, Activa, Bioqueri.

Figure. Poly gamma glutamate. N

Niacinamide (nicotinamide) http://www.skinactives.com/Niacinamide-Vitamin-B3.html

Niacinamide (vitamin B3) benefits skin color and decreases melanin synthesis (important for hyperpigmentation); decreases inflammation, itching (pruritus) and UV-induced skin cancers, and prevents immunosuppression by UV irradiation. By increasing NADPH, the donor of reducing power in cell biosynthesis, niacinamide will increase synthesis of collagen, involucrin, filaggrin, and keratin. This molecule is one of the components of NADPH (reduced niacinamide adenine dinucleotide phosphate) the coenzyme that provides the reducing power required to build new molecules in the human body. Niacinamide and niacin are not synthesized in the human body and therefore must be supplied externally (these is why we call niacin a vitamin), either through the diet or through topical application (or better, both). Niacinamide is also part of NAD (like NADP but without the extra phosphate), the molecule that is wherever carbohydrates and other foodstuffs are oxidized (respired) to make energy. Even when following a normal healthy diet, topical application of niacinamide will result in increased synthesis of collagen, keratin, involucrin and flaggrin. Topical application of niacinamide will decrease pruritus and inflammation, help acne affected skin, decrease oiliness, alleviate atopic dermatitis, decrease UV-induced skin cancers and help decrease facial pigmentation. These are just a few of the beneficial effects of topical application of niacinamide to the skin, and it would be suspicious that there are so many were it not for the crucial role of this chemical in human metabolism.
Namazi, Mohammad R. (2007) Nicotinamide in dermatology : a capsule summary.International Journal of Dermatology, 46:1229-1231. Bissett, Donald L.; Oblong, John E.; Berge, Cynthia A. (2005) Niacinamide: a B vitamin that improves aging facial skin appearance. Dermatologic Surgery, 31: 860-865.

Figure. Niacinamide.

Figure. NADPH Nobiletin (3',4',5,6,7,8-hexamethoxyflavone) http://www.skinactives.com/Nobiletin.html Nobiletin inhibits synthesis of the type of fats (triglycerides) that is food for the acne bacterium and slows down proliferation of fat cells. It also has antibacterial and fungistatic activity. I think that in the near future you will hear a lot more about nobiletin, which also seems to have antiaging and anti-tumor activity. Use at 2%, although you will probably need less if you use other actives that work on sebum secretion and acne.
Johann, S., de Oliveira V.L., Pizzolatti, M.G., Schripsema, J. Braz-Filho, R. Branco, A., Smnia A. Jr (2007) Antimicrobial activity of wax and hexane extracts from Citrus spp. Peels. Memorias Instituto Oswaldo Cruz: 102: 681-685 Sato T, Takahashi A, Kojima M, et al. (2007) A citrus polymethoxy flavonoid, nobiletin inhibits sebum production and sebocyte proliferation, and augments sebum excretion in hamsters. J. Inv. Dermatology, 127: 2740-2748

Figure: Nobiletin.

O Oryzanol (gamma) http://www.skinactives.com/Gamma-Oryzanol.html Gamma oryzanol is a UV absorber, anti-inflammatory, antioxidant, cancer preventive, and skin lightener. The name "oryzanol" comes from Oryza sativa, rice. This complex of ferulic acid esters is extracted from rice bran oil. The chemical structure of this complex gives it biological properties similar to those of ferulic acid but it dissolves easily in oil or creams.

Oka, T., Fujimoto, M.; Nagasaka, R., Ushio, H., Hori, M., Ozaki, H. (2010) Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol, attenuates mast cell degranulation. Phytomedicine, 17: 152-156.

Go to top P Passion Fruit (Passiflora edulis) Seed extract Other names: maracuja, granadilla. Passion fruit extract containing high concentrations of piceatannol (3,4,30,50-tetrahydroxytrans-Stilbene) inhibited synthesis of melanine and promoted synthesis of collagen. Passion fruit seed oil contains a high amount of unsaturated fatty acids with linoleic acid and oleic acid (14.4%) along with palmitic acid and stearic acid as main fatty acids.

Peptides Dermagen - http://skinactives.com/products/dermagen.htm Natural Active Peptides - http://skinactives.com/products/natural_active_peptides.htm Palmitoyl pentapeptide - http://skinactives.com/products/matrixyl.htm Copper peptide - http://skinactives.com/products/copper_peptide.htm Argireline - http://skinactives.com/news/forum.htm Amino acids are relatively small molecules: the smallest is glycine, with just two carbon atoms; one of the carbons is in the acid group (COO-) and the other has the amino group (NH4+) attached to it. Other amino acids have longer carbon chains; some have a couple (instead of just one) of amino groups or acid groups. There are many amino acids, but only 20 are common in proteins. Nomenclature: dipeptide (two amino acids linked by a peptide bond), tripeptide (3), tetrapeptide (4), etc. When you don't remember the name of numbers in Greek, use oligopeptide (oligo= few). Peptides are usually represented by a sequence of letters, one for each amino acid, and sometimes by a sequence of three letters for each amino acid. The skin care industry tends to use synthetic peptides that mimic peptides occurring naturally and modifies them by attaching a fatty acid to one end. This fashion became possible thanks to methods initially developed to facilitate the work of scientists. Two of the peptide actives sold by SAS are natural, Dermagen and "natural active peptides" and contain peptides related to collagen, a protein that makes up a good part of the dermal matrix.

Dermagen, an easy-to-use solution of collagen peptides and hyaluronic acid, will provide the skin with building blocks for the very important dermal matrix. Mix it into anything that contains water and it will blend in immediately. "Natural active peptides" (a.k.a. marine peptides) is a powder soluble in cold water, made of just collagen peptides obtained by hydrolysis (breakdown) of collagen. Used as indicated, they will provide not just building blocks but also extra protection against water loss. In short, there is a use for each of the peptides. Use the palmitoyl pentapeptide as a signal; use Dermagen to provide building blocks. If you prefer a powder, go for the natural active peptides and, to be on the safe side, add the synthetic peptide as a signal to get your skin going. For healing, use copper peptide. PLEASE NOTE: Signal peptides like Matrixyl and argireline are used in parts per million (ppm) concentrations because signal peptides are required at very low concentrations. Synthetic peptides are very expensive, so waste would be silly and costly. Petrolatum Note: we don't sell or use petrolatum in SAS products but you can buy it in the supermarket (Vaselin, etc.). Petrolatum (petroleum jelly) was invented (or discovered, depending how you look at it) in the mid 19th century and has been used since then in skin care. The application for a patent was filed in 1872. We at Skin Actives dont have much use for petroleum jelly, because we deal with other aspects of skin health and you can always layer some very inexpensive store brand petrolatum on top of any SAS product, if you need to. Petroleum jelly is likely to continue to be a very useful ingredient when trying to prevent water loss from badly damaged skin. Petrolatum is the main ingredient in Mustela baby balm, great for babies, and is also used in thousands of products all over the world. So if somebody tries to scare you just because petrolatum sounds like petroleum, tell them to go and read the scientific literature. Note: used in Crme de la Mer products. Phloretin http://www.skinactives.com/Phloretin.html Phoretin, a flavonoid, is responsible in part for the antioxidant activity of apples. Phloretin is a nice antioxidant and inhibits elastase activity; it also increases penetration of other actives. Phloretin has been shown to inhibit proliferation of breast cancer cells, and induces apoptosis (programmed cell death) in several types of cancer cells. Other flavonoids shown to be beneficial are chrysin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin.

Note: in SkinCeuticals Phloretin CF

Figure. Phloretin Pine bark proanthocyanidins http://www.skinactives.com/Pine-Bark-Proanthocyanidins.html

Proanthocyanidins (a.k.sa. condensed tannins) are polymers formed by the condensation of flavans In humans, these flavonoids protect capillary walls and inhibit the enzymes that break down collagen (collagenase), hyaluronic acid (hyaluronidase) and elastin (elastase). They also have anti-inflammatory and antiallergenic properties, and are free radical scavengers. Proanthocyanidins also help promote tissue elasticity, help heal injuries, reduce swelling and edema, restore collagen and improve peripheral circulation. Proanthocyanidins also prevent bruising, strengthen weak blood vessels and reduce histamine production. Note: this extract is also called pycnogenol.
See also grape seed proanthocyanidins. Fitzpatrick DF, Bing B, Rohdewald P. (1998) Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol., 32(4):509-15. Packer L, Rimbach G, Virgili F. (1999) Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med., 27(5-6):704-24.

Figure. Proanthocyanidins. Condensed tannins can be linear (with 48 bounds) or branched (with 46 bounds - dotted line).

Phytonadione (Vitamin K1) http://www.skinactives.com/Phytonadione-Vitamin-K1.html Phytonadione (a.k.a. phytomenadione; phytonadione) is the form of vitamin K found in plants. Vitamin K is a lipid-soluble vitamin required for the normal clotting of the blood. Phytonadione is the form of vitamin K used in newborns because it is safe (other forms of the vitamin can be problematic). Use a phytonadione cream if you have a tendency to bruise, have spider veins or after procedures such as laser or cosmetic surgery. It may also help alleviate rosacea symptoms. In some cases, it may help alleviate dark under-eye circles. In plants, it functions as an electron acceptor during phosynthesis, forming part of the electron transport chain of Photosystem I.

Figure. Phytonadione. Phytosterols http://www.skinactives.com/Phytosterols.html Phyotsterols include plant sterols and stanols, steroid compounds similar to cholesterol which occur in plants and vary only in carbon side chains and/or presence or absence of double bonds. Use phytosterols for dermatitis, atopic dermatitis, sunburn and psoriasis, together with

superoxide dismutase, antioxidant booster (with vitamin E) and bisabolol. Phytosterols have antiirritation and anti-inflammatory activity; they will help repair damaged skin and condition both skin and hair; will also regulate and normalize turnover of skin cells and improve dry skin. Phytosterols can help with skin damage produced by radiotherapy, and with scars and keloids. Stigmasterol has skin lightening activity and may prevent some types of skin cancer.
Wang, Tong; Hicks, Kevin B.; Moreau, Robert. (2002) Antioxidant activity of phytosterols, oryzanol, and other phytosterol conjugates. Journal of the American Oil Chemists' Society 79: 1201-1206.

Figure. Beta sitosterol. Polypodium leucotomos extract (PLE) http://www.skinactives.com/Polypodium-Leucotomos-Extract-PLE.html Polypodium is a fern, a relatively primitive plant that represents a bridge between green algae and higher plants. This evolutionary position means that some of the biochemicals found in Polypodium are very different from what you would find in flowering plants (although others, like rutin and kaempferol are also present in both PLE and many higher plants). Polypodium is a genus of between 75-100 species of true ferns, widely distributed throughout the world, with the highest species diversity in the tropics. Polypodium leucotomos (a.k.a. Phlebodium decumanum) grows in Ecuador and Honduras. Study of the many biochemicals present in this fern is a time-consuming process and we dont know yet which components are responsible for the medicinal properties of PLE, although calagualine, a saponin, have been mentioned as responsible for the inhibition of tumor necrosis factor (TNF)-induced activation of nuclear transcription factor-B, thus blocking tumor metastasis, proliferation, and inflammation. Psoriasis is one of the many diseases caused by the immune system, which should defend us from bacteria, viruses and other external agents, but sometimes goes haywire. PLE may suppress psoriasis by inhibiting the production of inflammatory cytokines. PLE also protects from the effects of UVA radiation when taken orally or applied topically, and inhibits inflammation caused by long exposure to UVB radiation, so even for those who dont have to worry about skin immune problems, PLE may help and in preventing photoaging by

improving membrane integrity, inhibiting metalloproteinases and reversing the loss of normal elastic fibers associated with skin aging. As more scientists and doctors learn of the multiple actions of PLE, it is tested on more diseases that involve disruption of the immune system or the inflammatory process, like atopic dermatitis and vitiligo. In short, PLE is a beautiful package that can improve the lives of many people. We at SAS are very proud to be able to offer you such a great active.
Gonzalez S; Pathak M A; Cuevas J; Villarrubia V G; Fitzpatrick T B (1997) Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatology, photoimmunology & photomedicine, 13: 50-60. Jimenez D; Naranjo R; Doblare E; Muoz C; Vargas J F. Anapsos (Polypodium leucotomos extract), an antipsoriatic drug, in atopic dermatitis. (1987) Allergologia et immunopathologia, 15: 185-9. Sempere, J. M.; Rodrigo, C.; Campos, A.; Villalba, J. F.; Diaz, J. (1997) Effect of Anapsos (Polypodium leucotomos extract) on in vitro production of cytokines. British Journal of Clinical Pharmacology, 43: 85-89.

Figure. Polypodium, a fern. Pomegranate extract. http://www.skinactives.com/Pomegranate-Extract.html This is an extract of the Punica granatum fruit. Contains betulinic acid, ellagic acid, gallic acid, malic acid, ursolic acid, polyphenols, all of these very active chemicals that together combine cancer preventive, antibacterial, antiviral, anti-inflammatory and many other beneficial properties.

Figure. Pomegranate by Otto Wilhem Thom, 1885.

Pomegranate (Punica granatum) seed oil http://www.skinactives.com/Pomegranate-Seed-Oil.html

The Latin name of the plant is Punica granatum, granatum for grained apple, Punica because the tree was introduced to Rome from Cartaghe (remember the Punic wars?). Anticancer properties of pomegranate seed oil may be derived from the high concentration of conjugated linolenic acids, fatty acids that contain double bonds alternating with single bonds in between. Pomegranate seed oil contains more than 70% cis9, trans11,cis13-18:3fatty acid. This kind of fatty acid composition is very rare and justifies the use of pomegranate seed oil, which is very expensive mainly because you need lots of pomegranates to get a very small amount of oil. Pomegranate seed oil is a chemopreventive for skin cancer and, very important, it has shown significant inhibition of proliferation of metastatic breast cancer cells, both estradiol-dependent and estradiol independent. Pomegranate seed oil causes breast cancer cells to go to apoptosis (self-destruct). The anti-metastatic effect may be through its anti-angiogenic potential. The oil is also cytotoxic to human monocytic leukemia cells. Porphyridium extract The extracellular polysaccharide produced by this red (Rhodophyceae) microalga has sulfate groups attached to the backbone are also non-reducing terminal D-xylopyranosyl and galactopyranosyl residues. It is known that this polysaccharide has antioxidant and anti-

inflammatory properties, and the xylitol residues may be responsible in part for the antiinflammatory properties (we use xylitol in our anti-inflammatory cream). Other properties: lifting, anti-wrinkle.
Tannin-Spitz, T.; Bergman, M.; van-Moppes, D.; Grossman, S.; Arad, M.S. Antioxidant activity of the polysaccharide of the red microalga Porphyridium sp. J. Appl. Phycol. 2005, 17, 215-222. Matsui, S.M.; Muizzudin, N.; Arad, S.; Marenus, K. Sulfated polysaccharides from red microalgae antiinflammatory properties in vitro and in vivo. Appl. Biochem. Biotechnol. 2003, 104, 13-22.

Figure. Porphyridium Pterostilbene is very similar in structure to resveratrol, but pterostilbene has a great advantage: better bioavailability. Among the properties of our new active are anti-inflammatory, anti-skin cancer (chemopreventive), anti-melanoma, antioxidant and antiglycation. You may remember that proteins, including those in our skin, lose functionality when their structure is altered by glycation (addition of sugars), one of the reasons why diabetic skin will age faster. Pterostilbene is also antibacterial and fungicide making it an all-rounded active which we will have to add to many of our products.

Figure. Pterostilbene

Figure: Kino tree of India (From Koehler, 1887). Extracts from various parts of this tree have been used for centuries in Aryuvedic medicine. The root is used as a source of pterostilbene. Q Quercetin This is a naturally occurring flavonoid (from the polyphenol group of compounds) compound found in most plant tissues and it has anti-cancer, anti-ulcer, anti-allergy activity, antiviral, and anti-inflammatory effects that have been attributed to quercetin's antioxidant activity. Applied topically, was found to protect crucial cell antioxidant systems, including glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase activities against damage from UVA irradiation. Quercetin will protect skin cells from oxidative stress induced by glutathione depletion, in synergy with ascorbic acid, preventing the carcinogenic effects of some chemical

pollutants. It also inhibits membrane lipid of skin cells from peroxidation when exposed to UV light. Another interesting property of quercetin is its anti-elastase activity, i.e. it inhibits the activity of the endogenous enzyme responsible for the breakdown of elastin, a component crucial to skin elasticity. Quercetin also helps with allergy and inflammation; and this is why you will find it in our anti-inflammatory cream which helps with eczema without inducing skin atrophy (the way cortisone products do).

Figure: Quercetin

R Resveratrol Resveratrol (3,5,4'-trihydroxystilbene), a polyphenolic antioxidant found in grapes and red wine, blocks UVB-mediated activation of the factor NFkappa-B, and this is the mechanism of protection against photocarcinogenesis.

Plant polyphenols like verbascoside, resveratrol , polydatin, quercetin , and rutin benefit the skin with anti-inflammatory and wound healing activity through their interaction with growth factor receptors (and the cytoplasmic and nuclear pathways these receptors control) rather than thorugh direct redox properties.[Pastore et al., 2012, Antioxidants & Redox Signaling, 16: 314-328].

Adhami, V.M. ; Afaq, F.; Ahmad, N. (2003) Suppression of ultraviolet B exposure-mediated activation of NF-?B in normal human keratinocytes by resveratrol. Neoplasia, 5:74-8 Wolter, F.; Stein, J. (2002) Biological activities of resveratrol and its analogs. Drugs of the Future, 27: 949-959. Bernard, P.; Berthon, J.-Y.(2000) Resveratrol: An original mechanism on tyrosinase inhibition International Journal of Cosmetic Science 22: 219-224.

Retinyl Acetate Vitamin A is absorbed through the skin and increases the rate of skin turnover, and gives an increase in collagen resulting in a more youthful appearance. Retinoids (retinoic acid, retinol, retinyl esters) inhibit synthesis of matrix proteases, increase collagen synthesis, stimulate division of keratinocytes and fibroblasts, and stimulate synthesis of extracellular matrix by fibroblasts.
Me E Me E E Me E OH Me Me

J.J.J. Fu, G.G. Hillebrand, P. Raleigh, J. Li, M.J. Marmor, V. Bertucci,_P.E. Grimes, S.H. Mandy, M.I. Perez, S.H. Weinkle and J.R. Kaczvinsky (2010). A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamidepeptideretinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen. British J. Dermatology, 162: 647654

Rhodiola rosea extract (Roseroot, Golden Root, or Arctic Root) This extract has been used for centuries to help with stress, but it also benefits the skin through

several chemicals including rosavin, salidroside and many more. Also known as Roseroot, Golden Root or Arctic Root, this extract is a brownish powder that contains a variety of excellent active chemicals, including rosavin, ?-sitosterol and gallic acid. You will find lots of different claims, but I chose it for its antioxidant properties. The more antioxidants, the merrier, especially if you live in a busy city. Rhodiola rosea root extract is also used in Skyn Arctic Brightening Serum Glo Peptide and Defense Serum, Exotica Rhodiola and High Potency Amine Complex Face Lift by Perricone.
Calcabrini, C., De Bellis, R. , Umberto, L., Potenza, L. De Sanctis, R., Patrone, V., Scesa, C., Dacha, M. (2010) Rhodiola rosea ability to enrich cellular antioxidant defences of cultured human keratinocytes . Archives of Dermatological Research. 302; 191-200 Gupta, A., Kumar, R. Upadhyay, N.K., Pal, K., Kumar, R., Sawhney, R.C. (2007) Effects of Rhodiola imbricata on dermal wound healing. Planta Medica, 73: 774-777. Note: Rhodiola rosea extract can be found in Origins Youthtopia firming cream, Rhonda Allison Exotica Rhodiola cream, Korres quercetin eye cream

Riboflavin (Vitamin B2) Riboflavin is a key component of the cofactors FAD and FMN, required by all flavoproteins, which play important roles in the electron transport chain (respiration). Also, decarboxylation of pyruvate and -ketoglutarate requires FAD; and fatty acyl CoA dehydrogenase (in fatty acid oxidation) also requires FAD

Figure. Riboflavin. Rose Hip Oil. http://www.skinactives.com/Rosehip-Seed-Oil-cold-pressed.html This organic, cold pressed oil is made fresh from the seeds of the wild rose (Rosa affinis rubiginosa) that grows in Chile. What is so special about this oil? Rose hip oil is a concentrated solution in linoleic (41%) and linolenic acid (39 %), two essential fatty acids that are found in the structural lipids of the cell but humans cannot make them. It also contains, tocopherols and carotenoids (responsible for the lovely pink/orange color of the oil). In clinical studies with humans, rose hip oil was effective in aiding tissue regeneration in surgical wounds and in treatment of keloids. Royal jelly NOTE: do not use this active if you are allergic to bees. http://www.skinactives.com/Royal-Jelly.html Royal jelly is a thick and milky secretion from the hypopharyngeal and mandibular glands of young worker bees (Apis mellifera L.) and is used to feed the larvae. The queen honeybee is fed royal jelly throughout the larval period, while nurse honeybees are fed royal jelly for only 3 days Royal jelly is a bit magical, probably because of its effect on the development of bees: feeding larvae with a continuing diet of royal jelly will make a larva develop into a queen bee rather than a drone or a worker. Actually, the mechanism of action of royal jelly on larvae is not magic but is caused by the presence of a peculiar protein that promotes epigenetic methylation of DNA. It still feels like magic to me. Royal jelly will not make us into queens, but it contains a variety of proteins, amino acids, organic acids, steroids, esters, phenols, sugars, minerals, vitamins, trace elements and other constituents (the composition varies with seasonal and regional conditions). Vitamins of the group B (pantothenic acid and pyridoxine) plus proteins, trace minerals and other goodies may have made a difference when vitamins were no readily available and may be the reason why royal jelly has so many traditional uses. Another interesting component of royal jelly is a fatty acid, 10-hydroxy-2-decenoic acid (10HDA), which seems to inhibit the vascularization of tumors. In skin, this fatty acid induced synthesis of involucrin, transglutaminase-1 and filaggrin, increased hydration of dry skin, activated keratinocyte differentiation, restored skin barrier function and reduced inflammation.

Figure: 10-hydroxy-2-decenoic acid (10 HAD) Rutin This flavonoid, abundant in Viola tricolor, Sophora japonica, Morus alba and many other plants, has numerous beneficial properties. Besides its anti-inflammatory and antiviral effects, it protects capillaries from oxidative stress preventing fragility.

Figure: Rutin. S Salicylic acid This weak acid (called beta hydroxy acid in the skin care industry "just because"), is used in exfoliation and to control acne. It is frequently dissolved in alcohol, drying the skin, but better formulations (like what we use in Skin Actives) avoid alcohol and allow salicylic acid to benefit the skin.

Figure. Salicylic acid

Saw palmetto http://www.skinactives.com/Saw-Palmetto.html Saw Palmetto (Serenoa repens) is well known as a natural remedy for benign prostate hyperplasia. Saw palmetto sterols have been shown to inhibit 5alpha-reductase activity, the enzyme responsible for conversion of testosterone to dihydrotestosterone and to inhibit binding of dihydrotestosterone to the cytosolic androgen receptor. This can be especially helpful for stubborn acne cases where DHT is a factor and when testosterone is responsible for male and female hair loss. Saw palmetto extract has been shown to be effective in some cases in minimizing hirsutism, the excessive growth of thick dark hair in locations where hair growth in women usually is minimal or absent.

Figure. Saw palmetto. Sea buckthorn berry oil Hippophae rhamnoides Ayurveda, Chinese and Tibetan traditional medicines used sea buckthorn to cure a variety of ailments, including healing of stomach ulcers, skin cancer, healing of burns, etc. Some of these uses are backed by scientific evidence showing that the plant contains chemicals valuable for human health. The oil pressed from the pulp of the fruit cotains palmitoleic (16:1n-7), palmitic (16:0) and oleic acids as the major fatty acids, plus many antioxidants including alpha-tocopherol (vitamin E). This oil promotes healing of wounds, also acts as UV protectant and retards ageing proces. Sea buckthorn seed oil has been shown to change on the fatty acid composition of skin glycerophopholipids of patients with atopic dermatitis, increasing the proportion of docosapentaenoic acid (22:5n-3) and decreased the proportion of palmitic acid (16:0).
Yang, B; Kalimo, KO; Tahvonen, RL; et al. (2000) Effect of dietary supplementation with sea buckthorn (Hippophae rhamnoides) seed and pulp oils on the fatty acid composition of skin glycerophospholipids of patients with atopic dermatitis J. Nutr. Biochem. 11:338-340.

Figure. Hippophae rhamnoides

Sea kelp bioferment (Lactobacillus/kelp ferment filtrate) (coral or ultramarine) http://www.skinactives.com/Sea-Kelp-Ultramarine.html This ferment obtained from sea kelp supplies a complete nutrient medium, and moisturizes skin and scalp. The substrate for fermentation is kelp, a sea macroalga (Phaeophyta). Fermentation makes the cell contents of this alga readily available to the scalp, moisturizing it and providing the nutrients required to synthesize new components. It also has anti-itch activity. This active is rich in fucoidan, caragenaan, algin, fucoxanthin, minerals and many active chemicals, will moisturize the skin and provide it with the nutrients required to synthesize new components. It provides minerals like iodine, copper, molybdate, magnesium, etc., required as cofactors in enzymatic reactions of lipid metabolism and energy conversion. Our Sea Kelp Bioferment can be used as a base for any of our water soluble actives. It is one of our favorite ingredients and you will encounter it in practically all of our ready mixed products. It is nutritious and works perfectly as a mask or added to bath water. See also fucoidan and fucoxanthin.
Note: this is the miracle broth in Crme de la Mer products.

Figure: Sea kelp

Selenomethionine http://www.skinactives.com/Selenomethionine.html This chemical is a form of the amino acid methionine in which sulfur has been replaced by selenium, is a common food source of selenium and also the optimum carrier of this essential nutrient to your skin. It has been shown that selenomethionine has anti-melanoma activity. Selenomethionine seems to inhibit broad band UVB-induced p53 transactivation and protein accumulation and this effect correlates with reported protective effects of selenium against UVinduced DNA damage. This effect is also reflected in reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.
Burke KE, Combs GF Jr, Gross EG, Bhuyan KC, Abu-Libdeh H. (1992) The effects of topical and oral Lselenomethionine on pigmentation and skin cancer induced by ultraviolet irradiation. Nutr Cancer. 17:123-37.

Kim, Aeyung; Oh, Jang-Hee; Park, Jong-Min; Chung, An-Sik. (2007) Methylselenol generated from selenomethionine by methioninase downregulates integrin expression and induces caspase-mediated apoptosis of B16F10 melanoma cells. Journal of Cellular Physiology (2007), 212(2), 386-400. TraynorN.J.,. McKenzie R.C., Beckett G.J , Gibbs , N.K. (2006) Selenomethionine inhibits ultraviolet radiation-induced p53 transactivation Photodermatology, Photoimmunology & Photomedicine, 22: 297 303

Figure. Selenomethionine. Silymarin http://www.skinactives.com/Silymarin.html Silymarin, a heterogenous extract of Silybum marianum (milk thistle) may be as effective as RetinA without the irritation. Silymarin has multiple beneficial effects on the skin, protecting it from a variety of environmental agents. Research has shown that silymarin reduces the effects of toxins on epidermal cells; as an antioxidant, it prevents the oxidative damage to DNA caused by UV radiation, and it protects against chemically induced skin tumors in mice. Recent research looked at the mechanism by which silymarin prevents skin cancer and it seems that it normalizes the function of a deranged cell membrane receptor. These multiple functions make silymarin an ideal ingredient for skin care and skin cancer prevention. Note: For people who have used benzoyl peroxide (BPO) in the past (I hope none of our clients use it at present) silymarin may help inhibit BPO-induced skin edema, myeloperoxidase activity, and interleukin-1 protein levels in the epidermis, possibly helping prevent BPO-caused skin cancer.
Kitajima, S. and Yamaguchi, K. (2009), Silybin from Silybum Marianum Seeds Inhibits ConfluentInduced Keratinocytes Differentiation as Effectively as Retinoic Acid without Inducing Inflammatory Cytokine J. Clinical Biochem. & Nutrition, 45: 178-184

Figure. Silybum marianum Sodium PCA. http://www.skinactives.com/Sodium-PCA.html Sodium pyroglutamate. This derivative of glutamic acid is very hygroscopic. It is naturally produced by our bodies and one of the components of "natural moisturizing factor", which our skin produces to slow down water loss to the environment. Sodium PCA is used as a moisturizer in skin care, and as a hair conditioner.

Figure. Pyroglutamic acid. Soy isoflavones http://www.skinactives.com/Soy-Isoflavones.html

In Korean folk medicine, soybean paste was applied to lacerated skin wounds, in the belief that it would accelerate wound healing and decrease scarring. Modern science has corroborated those beliefs and shown the broad scope of the beneficial effects of soy isoflavones on skin. For example, soy isoflavones genistein and daidzein were found to stimulate the synthesis of hyaluronic acid, preventing damage to the skin structure caused by natural loss of this structural component. Genistein induces collagenation in soft tissue wound healing and inhibits of tyrosine kinase, angiogenesis, and topoisomerase II and seems to inhibit tumor progression. In mice, genistein inhibited the initiation and promotion of two-stage skin carcinogenesis and ultraviolet light-induced oxidative events Isoflavones are polyphenolic compounds that are capable of exerting estrogen-like effects, i.e. they will bind to the estrogen receptors. For this reason, they are classified as phytoestrogens compounds with estrogenic activity derived from plants. Legumes, particularly soybeans, are the richest sources of isoflavones in the human diet. In soybeans, isoflavones are present as glycosides (bound to a sugar molecule). Fermentation or digestion of soybeans or soy products results in the release of the sugar molecule from the isoflavone glycoside, leaving an isoflavone aglycone. Soy isoflavone glycosides are called genistin, daidzin, and glycitin, while the aglycones are called genistein, daidzein, and glycitein, respectively (chemical structures of isoflavone aglycones).
Rocquet, C. and Bont, F. (2002) "Molecular aspects of skin aging - recent data". Acta Dermatovenereologica Alpina, Pannonica et Adriatica. Vol 11, No 3. Brincat, M. P.; Baron, Y. Muscat; Galea, R. (2005) "Estrogens and the skin." Climacteric, 8: 110-123.

Squalane (from Olive) Squalane is a good alternative to mineral oil. Loss of skin lipids result in an increased water loss and increased penetration of harmful compounds, especially for people living in big cities. Continuous use of Olive Extract should alleviate skin dryness and sensitivity. Whether used to repair damaged skin or merely to maintain already healthy skin.

Superoxide Dismutase http://www.skinactives.com/Superoxide-Dismutase-SOD.html Superoxide radicals are formed in a number of metabolic reactions, including lipid peroxidation initiated by light or metal ions. This process is the cause of rancidity of oils, but it also happens

in live tissues and may be a cause of cancer, inflammatory diseases, atherosclerosis, aging, etc. One of the reasons why the superoxide radicals are so dangerous is because they start chain reactions where more and more free radicals are formed, reacting with all cell constituents and breaking havoc wherever they go. In the human body, the main chain breaking antioxidants are the water soluble superoxide dismutase (SOD) and the lipid soluble alpha-D-tocopherol (vitamin E). SOD is a particularly stable enzyme that converts the destructive superoxide radical into a less dangerous form, hydrogen peroxide (which will, in turn, be converted into water and normal oxygen by the enzyme catalase). In our cells, we have our own SODs, but we can protect our skin by supplementing them with topically applied SOD. The size of the SOD used in skin care varies between 10,000 and 30,000 molecular weight, relatively small for an enzyme but large enough to be excluded from live cells. The fact that SOD is unlikely to enter live cells is not a problem. Lipid peroxidation occurs everywhere in the skin, not just in the live cells. The role of SOD is to eliminate the free radicals resulting from lipid peroxidation and to prevent the chain reactions that would eventually reach deeply into the skin, and topical application of SOD will certainly help to achieve this aim. T Tamanu oil (also called foraha or doomba oil) is pressed from nuts of the Calophyllum tacamahaca (or ati) or Calophyllum inophyllum tree. The nuts yield 7075% of the greenishyellow inedible oil. The oil originates in Polynesia where it continues to play an important cultural role. Typical fatty acid composition of tamanu oil: linoleic acid (38%), oleic acid (34%), Stearic acid (13%), palmitic acid (12%). Composition varies with environmental conditions but, in general, there is a majority of unsaturated fatty acids. Also present are phytosterols, mainly stigmasterol and beta-sitosterol.

Figure. Tamanu Calophyllum inophyllum - fruits Tea (Camellia sinensis L. KUNTZE), a.k.a. green tea

Green, black, and oolong teas -- along with coffee, red grapes, kidney beans, raisins, prunes, and red wine -- contain large quantities of polyphenols. Polyphenols, which are a class of bioflavonoids, have been shown to have antioxidant, anticancer, antibacterial, and antiviral properties. Most of the polyphenols in green tea are catechins. Catechins, which are antioxidants by nature, have also been shown to function as anti-inflammatory and anticancer agents. One of the major catechins in green tea, Epigallocatechin 3-gallate (EGCG), has been shown to be one of the most effective agents against skin inflammation and cancerous changes in the skin. Tea also conteins caffeine, very useful to depuff puffy eyes and cellulite. Tea tree (Manuka) essential oil http://www.skinactives.com/Tea-Tree-Essential-Oil.html The Melaleuca alternifolia essential oil that help with acne and fungal infections, probably because of its broad-spectrum antimicrobial activity, including fungi. Cineole and terpinene appear to be the key medicinal components in tea tree oil; terpin-4-ol and alpha-terpineol may help alleviate the edema associated with contact hypersensitivity. Terpin-4-ol was also shown to be effective in controlling the histamine- induced edema often linked to some allergic reactions. Because of its astringent effect tea tree oil helps keep the skin clean and fresh. Teprenone a.k.a. geranylgeranylacetone This is a chemical used in Japan for the treatment of gastric ulcer. Teprenone was not used in the USA for this or any other purpose until... yes, you guessed right! Teprenone started to appear in skin care products. The mechanism of action of teprenone on gastric ulcers is still unclear, but may involve increased synthesis of heat shock proteins. We simply don't know enough about its benefits or side effects. This story reminds me of a recent Judge Judy case, with a man who made his living as a research subject for pharmaceutical research. He called it an "easy way to make a living". Judge Judy explained to him (as nicely as she could) why he was a fool. This man was being paid to be a research subject, but why would anyone test novel chemicals and pay for the "privilege"? Thiamine (vitamin B1) Another example of a vitamin that is required in human metabolism, in this case thiamine pyrophosphate ia a coenzyme in the catabolism of sugars of amino acids.

Tocopherol (alpha-D). You will find tocopherol (plus much more) in our antiox booster http://www.skinactives.com/Antioxidant-Booster.html This is the natural form of vitamin E, an antioxidant that stimulates the immune system. The requirement for vitamin E was detected when scientists found that, unless it was present in the diet, pregnancy (in laboratory rats) could not be completed. Indeed, the name "tocopherol" derives from the Greek words for childbirth (tos), and to bring forth (phero). Vitamin E serves as a scavenger for free radicals that are destructive to the cell membrane, whose integrity is paramount to cell metabolism and life. Although alpha-D-tocopherol is the most widespread vitamin E, other tocols are also vitamin E, in the sense that they have vitamin E activity. The only difference between tocotrienols and tocopherol is that tocotrienols have three double bonds in their side chain and have a higher antioxidant activity. We use alpha-D-tocopherol in conjunction with other lipophilic antioxidants (see our antiox booster), they work better together. The ozone present in polluted air decreases Vitamin E content in the stratus corneum, accelerating oxidation and destruction of membrane lipids, which in turns causes skin problems. This is why it is important to apply alpha-D-tocopherol topically to replenish the Vitamin E lost by the action of ozone on skin. Note: Synthetic forms of this chemical can be allergenic.

Figure: alpha D-tocopherol Tetrahydrocurcuminoids http://www.skinactives.com/Tetrahydrocurcuminoids.html

Purified curcuminoids from tumeric (Curcuma longa), strong yellow in color, are modified chemically to increase its biological availability and to turn them white, making them more suitable for use in skin care products. Curcuminoids extracted from the rhizomes of Curcuma longa (turmeric) have great antioxidant and anti-inflammatory properties that make them almost ideal ingredients for skin care. Their molecular structure is the reason for the potent antioxidant properties they possess, but because of their low solubility and poor bio-availability, very high concentrations are required to obtain the desired effects. Also, curcuminoids strong yellow color makes it difficult to employ in high concentrations in cosmetic formulas. Scientists realized that the small amounts that were absorbed and used, were eventually converted by the body into a much better chemical, tetrahydrocurcuminoids (THCs), so they decided to do the chemical conversion (hydrogenation) in the laboratory, before applying it to the skin. Thus the yellow, low bio-availability curcuminoids are converted in the lab into the colorless, highly soluble THCs. Tetrahydrocurcuminoids keep the superior antioxidant and anti-inflammatory properties of curcuminoids, but are easier to use in skin care products. Skin lightening, anti-oxidant, anti-inflammatory

O CH 2 HO OMe CH 2 C CH 2

O C CH 2 CH 2 OH OMe

Note: Products that contain curcuminoids include Shiseido Revital Neck Zoom Essence, Shiseido Revital Wrinklelift Retino Science AA

Thioredoxin. http://www.skinactives.com/Thioredoxin-TRX.html Thioredoxins are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange. Thioredoxins are found in nearly all known organisms and are essential for life in mammals This is an enzyme I became familiar with in my days as a plant biochemist, long before Wikipedia (or the internet, for that matter) was invented, because thioredoxin is "everywhere",

including the regulation of the most abundant protein on earth, Rubisco, the enzyme that "fixes" carbon dioxide making life possible for every plant and animal (including us). Thioredoxin will make sure that the chain of events keeping proteins in their "right" reduction state is kept well oiled. Or, in other words, thioredoxin will facilitate the reduction of your skin proteins by cysteine (in a disulfide bond|thiol-disulfide exchange). The Trx (thioredoxin) and Grx (glutaredoxin) systems control cellular redox potential, keeping a reducing thiol-rich intracellular state, which on generation of reactive oxygen species signals through thiol redox control mechanisms. Skin Actives uses many valuable antioxidant chemicals can be purified from plants, e.g. astaxanthin, alpha-D-tocopherol and resveratrol, but they cannot replace the need for antioxidant enzymes, which are proteins.

Figure. Ribbon model of thioredoxin. Note: Thioredoxin is in the ingredient list for Cosmedix Affirm and in RX UV recovery.

Tocotrienols You will find tocotrienols (plus much more) in our antiox booster http://www.skinactives.com/Antioxidant-Booster.html Tocotrienols (alpha, gamma and delta) are very similar to tocopherol, but they have three double bonds in their isoprenoid side chain. The extra double bonds in the chemical structure of tocotrienols make them more powerful antioxidants and UV-protectants than tocopherol. They also give the molecule a better insertion into the lipid bilayer that is the core of every single

biological membrane. The antioxidant activity of tocotrienols is likely to be the underlying mechanism of their tumor suppressing activity. Tucuma butter Astrocaryum vulgare is a palm native to the Amazonian rainforest. The butter is extracted from its fruit and is rich in lauric, myristic and oleic acids plus some "extras" like vitamin A. Tucuma butter has emollient and skin softening properties.

Figure. Tucuma (Astrocaryum vulgare)

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U Ursolic acid has anti-inflammatory, antitumor, and antimicrobial properties. Ursolic acid is present in many plants, especially in extracts of pomegranate, rosemary, Greek sage (Salvia triloba), oleander, periwinkle, spike lavender, etc. Through the inhibition of human leukocyte elastase, an enzyme that catalyzes rupture of the cell membranes in inflamed tissues, ursolic acid inhibits inflammation and maintains structural integrity of cells and the intercellular matrix. It also inhibits 5-lipoxygenase and cyclooxygenase activity. Ursolic acid increases ceramide and collagen and preserves the structure of collagen fibers. These properties, together with its inhibition of elastase activity, makes it a good antiaging and anti-wrinkle ingredient. Other activities reported for ursolic acid include: antihistaminic, antiviral, cancer preventive. Wheat germ oil

Cold pressed from the germ (embryo) of the wheat kernel. It contains some good fatty acids, including linoleic acid (omega-6), palmitic acid, oleic acid and linoleic acid (omega 3), and a wax (octacosanol). It is also very rich in vitamin E and also contains vitamins A, B, D, lecithin and
antioxidants.

White willow extract (salicin) http://www.skinactives.com/Willow-Bark-Extract-Salicyn.html Since Hippocrates times, white willow bark has been used to ease aches and pains and reduce fevers. The active chemical is salicin, an alcoholic -glucoside.

Figure. Salicin.

Wild yam (Dioscorea villosa) http://www.skinactives.com/Wild-Yam-Diosgenin.html See also Elixir10 Wild yam extract decreases melanin synthesis, and of the unique chemicals in yam, diosgenin has anti-inflammatory and anti-tumor properties, and dioscorin is an antioxidant. Diosgenin has affinity for the estrogen receptors.

Figure. Dioscorea villosa Willowherb (Epilobium angustifolium) The main bioactive molecule found in Canadian willow herb extract is oenothein-B. This molecule has been patented for its wide ranging bioactivity including anti-viral, antitumor, and

anti-hyperandrogenic applications and also has demonstrated free radical scavenging ability. It has been shown that the extract kills Propionibacterium acne, the bacterium associated with acne. Witch-hazel (Hamamelis virginiana) extract This plant extract contains a collection of chemicals with medicinal properties, including gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and many more that explain why this herb has been used for centuries as an astringent, pain-killer, for bruises and inflammatory swellings, etc. Z Zinc PCA (see also sodium PCA) http://www.skinactives.com/Zinc-PCA.html Many thanks to our clients who suggested we start selling zinc as an active. We chose to the zinc salt of L-pyrrolidone carboxylic acid (L-PCA), a.k.a. Zinc PCA. The mechanism of action of Zinc may still be a matter of discussion, but there seems to be an agreement that salts of this metal decrease inflammation caused by acne, maybe through inhibition of the enzyme that catalyses the production of dihydroxytestosterone, a hormone that controls sebaceous gland activity. Zinc is also an antibacterial, and its salts are used to control dandruff. Antibiotics can be useful in the treatment of acne, but in some circumstances antibiotics may not be an option, plus it is a bad idea to use them for long periods of time. Our clients suggested that Zinc could be a good addition to our SAS acne treatment regime, which includes SAS acne cream, T-zone serum and salicylic wash. We decided to offer zinc as zinc PCA. Zinc PCA may offer additional benefits to the skin. Lpyroglutamate, a derivative of glutamic acid (an amino acid) is very hygroscopic, meaning it absorbs large quantities of water. A relatively simple molecule, it is naturally produced by our bodies and is one of the components of "natural moisturizing factor", which our skin produces to slow down water loss to the environment. Zinc-PCA offers the benefits of PCA and those of the zinc and, maybe, something more. For example, zinc PCA (but not zinc alone) seems to decrease sebum secretion by oily skin. How to use our Zinc PCA solution: add to SAS salicylic wash for acne and oily skin. Mix with sea kelp bioferment to apply to scalp (seborrheic dermatitis, dandruff). Also add it to T-Zone serum or your favorite shampoos and conditioners.

Jarrousse, V.; Castex-Rizzi, N.; Khammari, A.; Charveron, M.; Dreno, B. (2007) Zinc salts inhibit in vitro toll-like receptor 2 surface expression by keratinocytes European Journal of Dermatology 17: 492496.

Nitzan, Yuval Bibi; Cohen, Arnon D. (2006) Zinc in skin pathology and care. Journal of Dermatological Treatment (2006), 17(4), 205-210.

Go to top Copyright Skin Actives Scientific LLC, 2013. Note: Figures of chemical structures were obtained from Wikimedia see http://commons.wikimedia.org/wiki/Commons:Welcome