Fitoterapia 84 (2013) 227236

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Fitoterapia
journal homepage: www.elsevier.com/locate/fitote

Review

Phytochemical and therapeutic potential of cucumber

Pulok K. Mukherjee a,, Neelesh K. Nema a, Niladri Maity a, Birendra K. Sarkar b
a b

School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India Parker Robinson (P) Ltd., 1, Nimak Mahal Road, Kolkata-700043, India

a r t i c l e

i n f o

a b s t r a c t
Cucumber (Cucumis sativus L.) is a member of the Cucurbitaceae family like melon, squash and pumpkins. It is a popular vegetable crop used in Indian traditional medicine since ancient times. This vegetable is very high in water content and very low in calories. It has potential antidiabetic, lipid lowering and antioxidant activity. Cucumber has a cleansing action within the body by removing accumulated pockets of old waste materials and chemical toxins. Fresh fruit juice is used for nourishing the skin. It gives a soothing effect against skin irritations and reduces swelling. Cucumber also has the power to relax and alleviate the sunburn's pain. The fruit is refrigerant, haemostatic, tonic and useful in hyperdipsia, thermoplegia etc. The seeds also have a cooling effect on the body and they are used to prevent constipation. Several bioactive compounds have been isolated from cucumber including cucurbitacins, cucumegastigmanes I and II, cucumerin A and B, vitexin, orientin, isoscoparin 2-O-(6-(E)-p-coumaroyl) glucoside, apigenin 7-O-(6-O-p-coumaroylglucoside) etc. Despite huge exploration of cucumber in agricultural field, comparatively very few studies have been published about its chemical profile and its therapeutic potential. This article reviews the therapeutic application, pharmacological and phytochemical profile of different parts of C. sativus. In this review we have explored the current phytochemical and pharmacological knowledge available with this well known plant and several promising aspects for research on cucumber. 2012 Elsevier B.V. All rights reserved.

Article history: Received 27 April 2012 Accepted in revised form 1 October 2012 Available online 23 October 2012 Keywords: Cucumis sativus Cucumber Cucurbitacins Phytochemistry Pharmacology

Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . 2. Origin and phyto-geography . . . . . . . . . . . . . . 3. Morphological characterization of different parts of plant 4. Phytochemical signicance . . . . . . . . . . . . . . . 5. Pharmacological activity and therapeutic benets . . . . 6. Cucumber used in cosmetic . . . . . . . . . . . . . . 7. Concussion . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 228 228 228 232 234 235 235 235

1. Introduction Cucumber (Cucumis sativus L.), belongs to the Cucurbitaceae family. It is commercially cultivated worldwide as a seasonal vegetable crop. It is native to India, found wild in the Himalayas

Corresponding author. Tel./fax: +91 33 24146046. E-mail address: naturalproductm@gmail.com (P.K. Mukherjee). 0367-326X/$ see front matter 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.tote.2012.10.003

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from Kumaun to Sikkim and cultivated throughout the country with different vernacular names viz. cucumber (Eng.), Kheera (Hindi), Trapusha (Sanskrit), Shashaa (Beng.) and Vellarikkay (Tamil). Kirkbride (1993) has enlisted 70 synonymous for C. sativus [1]. It is widely consumed fresh in salads or fermented (pickles) or as a cooked vegetable [2]. Amongst 30 species of Cucumis, C. sativus has the most economic value [3,4]. The medicinal properties of the cucumber had been described since ancient times. Different parts of the plant viz. leaf, fruit and seed have been explored for their therapeutic benefits. C. sativus fruits and seeds (Fig. 1) have important therapeutic value in the Indian systems of medicine, particularly in Ayurveda where over 200 herbs, minerals and several formulations are available for management of aging [5,6]. They are widely used for various skin problems including swelling under the eyes and sunburn. It is believed that they promote refreshing, cooling, healing, soothing, emollient and anti itching effect to irritated skin [7]. In Chinese folk medicine the leaves, stems and roots are generally used as anti-diarrheal, detoxicant and anti-gonorrheal agents [8]. The leaves of the plant possess cooling and antioxidant effect. Several pharmacological activities including the antioxidant, antiwrinkle, antimicrobial, antidiabetic, and hypolipidemic potentials have been reported with this plant. Antihyaluronidase and anti-elastase activities have been proved for its cosmetic potentials [9]. Few bioactive compounds have been derived from this plant belonging to different chemical groups. Bitter principles Cucurbitacins (Cts) are the characteristic properties of this species. Despite the wide use of cucumber in folk medicine, very few studies have been reported in the scientific literature about its chemical consistency and its therapeutic activity [10]. In this review, we explore the current phytochemical and pharmacological knowledge about this well known plant species as well as several promising aspects for research on C. sativus. 2. Origin and phyto-geography The genus Cucumis holds great interest dates back to Linnaeus for the study of its evolution. Evolutionarily, Cucumis genomes are labile, therefore large genetic varieties of cucumber are found in different parts of the world. Genus Cucumis is having 2 types of subgenus. The first type of

subgenus was developed in the African region whereas another was developed in the Asian region [1,11]. Cytological study revealed that C. sativus is the only species in the genus with a chromosome number of n = 7, which evolved from a presumed ancestral karyotype with n = 12 [12]. There is much evidence to suggest that the cucumber is indigenous to Himalayan origin of northern India [3] and are domesticated in Asia [13]. In China, it is cultivated for at least 2000 years and occupies 2nd largest area among vegetables after Chinese cabbage. In India, this species has been cultivated with two forms: creeping form, cultivated in the field during hot season; and climbing form, cultivated during the rainy season [3]. Verities of Cucumber are conventionally separated in to four categories: (i) the exotic group of European and American cultivars; (ii) cultivar from the western part of India that are xerophytic in nature; (iii) Chinese cultivars with long fruits and glossy skin; and (iv) Himalayan type, mostly with rusty skin [3]. National Seed Corporation is promoting the Poinsett variety of cucumber which was introduced from the USA and now popular in northern India. It is highly resistant to downey mildew, powdery mildew, anthracnose and angular leaf spot. Poona Khira in Maharastra, Balam Khira in Uttar Predesh, Khira 95 and Khira 90 in Himachal Pradesh are the diverse varieties accepted by the cultivator at different regions in India. Indian Agricultural Research Institute (IARI), New Delhi developed some new varieties of cucumber such as DC-1, Sel. DC 2 (Pusa Uday), DC-3 etc. [14,15]. 3. Morphological characterization of different parts of plant Cucumber is an annually growing creeping vine. Its leaves are hispidly hairy tralling or climbing type. Leaves are simple alternate, deeply cordate 35 lobed in both surfaces with a hairy margin denticulate. Flowers are yellow in colour; male flowers are clustered, bearing anthers with cohering, connective crushed or elevated above the cells whereas females are solitary thick covered with very bulbous based hairs [16]. Fruits are compressed, elongated, ellipsoid, dorsiventrally convex and laterally ridged with variable size. Seeds are cream or white, testa hard and smooth. Cucumber has enclosed dcoyledonous seeds and it develops from a flower, and therefore it is classified as a fruit. Micropyle pointed, distinctly visible; outer most layer of testa is absent and each cotyledon shows five distinct patches of small, thin walled, polygonal cells [6]. 4. Phytochemical signicance Leaves, fruits and seeds of C. sativus contain numbers of phyto-constituents as shown in Fig 2. The presence of cucurbitacins (triterpenoid substances-well-known for their bitterness and toxicity), is the characteristic property of the family Cucurbitaceae. Structurally, Cts have a tetracyclic cucurbitane nucleus skeleton, namely, 9-methyl-19-nor lanosta-5-enea, which is arbitrarily divided into twelve categories [17]. Cucurbitacins A, B, C, D, E and I (16) were identified in cotyledons of different verities of C. sativus seedlings [18]. Cucurbitacins have been reported as the bitter principle in the Cucurbitaceae family [19]. On maturity of the fruits due to the effects of the enzyme elaterase cucurbitacins are hydrolyzed

Fig. 1. C. sativus fruits and seeds.

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229

[20] to its non bitter principles. The activity of the elaterase is usually controlled by two genes [21]; a dominant gene Bt [22] produces extremely bitter fruit, where as another recessive

gene bi [23] inhibits the formation of curcurbitacin in the foliage and fruit. Usually the bitter principal does not accumulate very heavily in the fruit. The amount of bitterness in cucumbers

Fig. 2. Phyto-constituants present in Cucumis sativus.

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OH

O HO O

OH OH

HO HO HO OH

H O

O HO OH OH OH HO

O OH OH OH O

(11) Orientin

(12) Isoorientin

OH OH OH O (13) Cucumegastigmanes I HOH2C O O OH O OH O OH

(15) (+)-Dehydrovomifoliol

OH OH (14) Cucumegastigmanes II H O N H (17) Indole-3-corboxylic acid O OH

N H (16) Indole-3-aldehyde

R2 OR3 HO HO HO O O OH HO R1
(18) (19) (20) (21) (22) (23) (24) Isovitexin 2-O-(6-(E)-p-cou maroyl) glucoside Isovitexin 2-O-(6-(E)-p-cou maroyl) glucoside-4-O-glucoside Isovitexin 2-O-(6-(E)-feruloyl) glucoside-4-O-glucoside Isoscoparin 2-O-(6-(E)-p-cou maroyl) glucoside Isoscoparin 2-O-(6-(E)-feruloyl) glucoside-4-O-glucoside Isovitexin 2-O-(6-(E)-feruloyl) glucoside Isoscoparin 2-O-(6-(E)-feruloyl) glucoside
Fig. 2 (continued ).

O H OH O O OH

OH

OH
R1 H H OCH3 H H OCH3 OCH3 R2 H H H OCH3 OCH3 H OCH3 R3 H Glc Glc H Glc H H

appears to vary from year to year and from location to location. This may occur because elaterase production is stimulated or depressed under certain environmental conditions such as cool

temperatures can enhance bitterness of the fruit [21]. Another study reveals that the bitterness of cucumber is caused mainly by cucurbitacin C but the amount was found in a very small

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231

R2 R1 O O HO OH
25. 25. 27. Saponarin Saponarin 4-O-glucoside Vicenin-2 R1 Glc Glc H R2 H H Glc

OR3 O

H OH OH

R3 H Glc H

O O HO HO OH O O OH OH O O

OH

28. Apigenin 7-O-(6''-O-p-coumaroylglucoside)

R OH HO O HO O OH O O OH OH OH OH OH O O O OH OH OH 32. Kaempferol 3-O-rhamnos O OH

29. Quercetin 3-O-glucoside R = OH 30. Kaempferol-3-O-glucoside R= H 31. Isorhamnetin-3-O-glucoside R=OCH3

Fig. 2 (continued ).

quantity (much less than 1 mg/100 g) even when selecting a strongly bitter fruit (threshold level of the bitterness is less than 0.1 mg/L). Total nitrogen and amine acid-N levels are the key

factors for promoting nitrogen metabolism in the leaf and fruit. High amount of total nitrogen favors the enzymatic synthesis of cucurbitacin C and affect the degree of bitterness [24]. Stem end

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of the fruits are comparatively richer of cucurbitacin C than the middle or blossom end of the fruit therefore it is general practice to cut the stem end first before consuming the fruits [19]. Fruits contain water (96.4%), protein (0.4%), fat (0.1%), carbohydrate (2.8%), mineral (0.3%), calcium (0.01%), phosphorus (0.03%), iron (1.5 mg/100 g) and vitamin B (30 IU/100 g). Enzyme crepsin, proteolytic enzyme, ascorbic acid, oxidase, succinic and malic dehydrogenase have also been reported in fruits [4]. Fruits contain a high concentration of ascorbic acid [25] whereas pulp and peel extracts contain lactic acid (~78% w/w), which showed antioxidant activity [2]. Sotiroudis et al., isolated essential oils and found 21 compounds including Z-6-nonenol (61.54%), E-2-nonenol (6.98%), E,Z-2,6-nonadienal (47.08%), E-2nonenal (17.39%), Z-3-nonenol (14.79%), 3-nonenal (7.32%), pentadecanal (43.47%), 9,12,15-octadecatrienal (14.52%) and 9,17-octadecadienal (12.33%) from three distinct cultivars [2]. Kemp et al., (1974) isolated volatiles from cucumber by steam distillation at 70 C mainly as 1-nonanol, trans-2-nonen-1-ol, cis-3-nonen-1-ol, cis-6-nonen-1-ol, trans, cis-2,6-nonadien-l-o1, cis, cis-3,6-nonadien-l-o1, cis-6-nonena1, cis-3-nonenal and cis, cis-3,6-nonadienal [26]. In another study with gas chromatographymass spectrometry (GC-MS), Zhou and Mcfeeters (1998), identified thirty seven volatile compounds from the fermented cucumber when it was treated with common salt (2% NaCl). Lipid and fatty acid composition of cucumbers and their altering amount during storage were also examined. It was found that fatty acids primarily lauric, myristic, palmitic, stearic, oleic, linoleic, tricosanoic, tricosenoic, lignoceric, and nervonic acids present in cucumber and their amount are increased when packed due to the diffusion of spice oils and loss of water [27,28]. Seeds are also rich by the number of constituents including crude proteins (42%) and fats (42.5%). The ash is rich with phosphate (P2O5, 0.62%). The extracted oil from seeds is clear and light yellow with specific gravity of 0.91; acid value 0.22; sopanification value 1930; soluble fatty acid (as butyric acid) 0.4% and unsopanification matter (0.91%). The fatty acid components are palmitic (0.63%), stearic (16.2%), linoleic (40.11) and oleic acid (38.70) [4]. It contains a number of sterols such as codisterol, 25 (27)dehydroporifersterol, clerosterol, isofucosterol, stigmasterol, campesterol, 22-dihydrobrassicasterol, sitosterol, 25 (27)dehydrofungisterol, 25 (27)-hydrocondrillasterol, 24--ethyl-25 (27)-dehydrofungisterol, avenasterol, 22-dihydrispinosterol and 24-methylenecolesterol [29]. The gibberellin hormone was also found in seeds [30]. Seed cake contains water (1.13%) protein (72.53%) ash (9.7%), crude fiber (1%) and carbohydrates (8.64%) [4]. Plant leaves are also sources for some major phytoconstituents. Vitexin-6-(4-hydroxy-1-ethylbenzene) (cucumerin A) (7) and isovitexin-8-(4-hydroxy-1-ethylbenzene) (cucumerin B) (8) are the two new major C-glycosyl flavonoids products, identified in the leaf tissue with some known flavonoids as apigenin 8-C--D-Glucopyranoside (vitexin) (9), apigenin6-C--D-glucopyranoside (isovitexin) (10), luteolin-8-C-D-glucopyranoside (orientin) (11), luteolin-6-C--D-gluco pyranoside (isoorientin) (12), and 4-hydroxycinnamic acid [31]. Kai et al., (2007) isolated two new megastigmane, cucu megastigmanes I [(6S,7E,9S)-6,9,10-trihydroxy-4,7-megastig madien-3-one] (13) and cucumegastigmanes II [(6S,7E,9S)6,9,10-trihydroxy-4,7-megastigmadien-3-one, 10-O--D-glu

copyranoside] (14) along with a known megastigmane (+)dehydrovomifoliol (15) from the leaves of C. sativus. Other five known compounds namely lutein; (+)-(1R,2S,5R,6S)2,6-di-(4-hydroxyphenyl)-3,7-dioxabicyclo (3,3,0) octane; indole-3-aldehyde (16); indole-3-carboxylic acid (17) and adenosine were also identified from the same [32]. A methanolic extract of fresh leaves of C. sativus, which when grown with potassium silicate and infected with Sphaerotheca fuliginea yielded five new acylated flavone C-glycosides identified as isovitexin 2-O-(6-(E)-p-coumaroyl) glucoside (18), isovitexin 2-O-(6-(E)-p-coumaroyl) glucoside-4-O-glucoside (19), isovitexin 2-O-(6-(E)-feruloyl) glucoside-4-O-glucoside (20), isoscoparin 2-O-(6-(E)-p-coumaroyl) glucoside (21), and isoscoparin 2-O-(6-(E)-feruloyl) glucoside-4-O-glucoside (22). The known flavone-glycosides isovitexin 2-O-(6-(E)feruloyl) glucoside (23) and isoscoparin 2-O-(6-(E)-feruloyl) glucoside (24), saponarin (25), saponarin 4-O-glucoside (26), vicenin-2 (27), apigenin 7-O-(6-O-p-coumaroylglucoside) (28) were also identified in this plant material [33]. Other phyto-constituents such as 4-X-O-diglucosides of isovitexin and swertiajaponin are identified and separated by preparative column chromatography from methanolic extract of the plant leaves. Quercetin 3-O-glucoside (29), kaempferol 3-O-glucoside (30), isorhamnetin 3-O-glucoside (31), and kaempferol 3-Orhamnoside (32) are other phyto-constituents were found in the methanolic extract of the flowers [34]. 5. Pharmacological activity and therapeutic benets The ethnomedicinal and therapeutic benefits of cucumber had been described since antiquity. The fruits are sweet, refrigerant, haemostatic and tonic. Therefore traditionally it is used for the wide spectrum of cure in rural and urban areas to remove general debility, and as a cooling agent. Usually cucumber fruits or seeds are used for treatment of skin problems through centuries [16]. Scientifically, very few works related to pharmacological activities have been reported till date. The pharmacological activities and works related to this species have been summarized in Table 1. Cucurbitacins present in C. sativus exhibited cytotoxicity and anti-cancer activity. Besides this, cucurbitacins also exhibited wide ranges of in-vitro or even in-vivo pharmacological effects and in used as purgative, anti-inflammatory and anti-fertility agent [35]. Cucumber extract showed antioxidant activities against various assays including DPPH reduction assay, total oxyradical scavenging capacity (TOSC) assay, trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) or ferric reducing-antioxidant power (FRAP) assays [3638]. Melo et al., (2006) reported the polyphenol contents in cucumber. Total phenolic contents, flavonols and proanthocyanidins were found to be 9.05 0.83, 2.06 0.09 and 55.66 1.52 mg/100 g respectively in cucumber extract. The whole extract contains high concentrations of ascorbic acid (1.49 0.85 mg/100 g) also [39]. Like one more study, free phenolics content in cucumber was found to be 14.37 1.48 mg/100 g of sample (73.8%), when it was examined along with another 10 vegetables [25]. In this experiment bound phenolic compounds as Bound-E and Bound-W were found to be 2.92 0.07 (15%) and 2.17 0.06 (11.2%) mg/100 g of sample respectively. High percentages of vitamin C (23.5%)

P.K. Mukherjee et al. / Fitoterapia 84 (2013) 227236 Table 1 Pharmacological activity of different part of Cucumis sativus. Pharmacological activity Antioxidant activity Year 2010 Parts/phytoconstituent Used Lyophilized juice of cucumber fruit Methanolic extracts of peel and pulp and juice Methanolic extract of seeds Cucumber cotyledons Assay/ Study DPPH-free radical scavenging activity Superoxide radical scavenging activity DPPH free radical scavenging activity DPPH free radical scavenging antioxidant potential Superoxide dismutase (SOD) Guaiacol peroxidase (POD) Ascorbic acid peroxidase (APX) Glutathione reductase (GR) Ferric reducing-antioxidant power (FRAP) assays Trolox equivalent antioxidant capacity (TEAC) test -carotene bleaching method Result/ Activity (IC50 = 35.29 1.30 g/ml) (IC50 = 14.73 1.42) EC50 = 1.84 0.1 (Peel) EC50 = 1.31 0.1 (Pulp) EC50 = 5.82 0.1 (Juice) 76.2% protective activity at concentration of 700 g/ml. Antioxidant -tocopherol and benzoquinone decreases the UV-B-induced enzyme SOD, POD, APX, and GR 0.71 mmol Fe2+/kg FW3 0.43 mmol Trolox/kg FW. Anti-oxidant activity 34.3% and 28.0% respectively due to total phenolic content 48.0 0.9 mg /100 g. 1.28 0.05 mol of vitamin C equiv/g of sample 100 mmoles Trolox Equivalents/100 grams of sample (TE) IC50 = 20.98 1.78 g/ml IC50 =6.14 1.74 g/ml SPF value 0.67 0.54 at concentration of 200 g/ml Lutein (IC50 = 170.7 M), and (+) -(1R, 2S, 5R, 6S) -2, 6-di-(4'-hydroxyphenyl)-3, 7dioxabicyclo [3.3.0] octane (IC50 = 270.8 M) decreased tyrosinase expression suppress melanogenesis and showed de-pigmentation 33.13% mushroom tyrosinase inhibition activity (MIC = 0.09-0.50 mg/mL) Staphylococcus aureus Staphylococcus epidermidis Escherichia coli Enterobacter cloacae Klebsiella pneumonia Pseudomonas aeruginosa MIC = 1.84-2.90 mg/mL Candida albicans Candida tropicalis Candida glabrata Bacillus cereus Escherichia coli Listeria monocytogenes Salmonella typhimurium 500 mg/kg/d for 15 days decrease the serum glucose and hepatic lipid peroxidation associated with the diabetes Decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak 5 g/kg body weight/day showed significant results Significant anti-ulcerogenic activity at dose of 300 mg/kg Anti-parasitic function may be presence of lectin

233

Ref. [9]

2010

[2]

2009 2004

[53] [54]

2003

Pulp residue treated with acetone and chloroform

[37]

2002

Cucumber ethanol and water extract Lyophilised acetone extract (80%) of fruits Fruits with peel Lyophilized juice of cucumber fruit Fruits MeOH extracts of leaves and stems

[42]

2002 2000 Antiwrinkle and antiaging activity 2010 2010 2008

Total oxy-radical scavenging capacity (TOSC) assay DPPH free radical scavenging activity Anti-hyaluronidase Anti-elastase activity Sun protective efficiency determination Inhibited melanin production in B16 cells

[25] [36] [9] [44] [45]

2007 Antimicrobial activity 2010

Ethyl acetate extract of fruit Volatile oil of cucumber (Cultivated in greenhouse at Crete; South Greece)

Anti-tyrosinase activity inhibition assay Antibacterial activity Gram-positive bacteria: Gram-negative bacteria:

[46] [2]

Antifungal activity Human pathogen fungi:

2004

Antidiabetic activity

2010

Phyto-constituents (E, Z)-2, 6-nonadienal (NDE) and (E)-2-nonenal (NE) present in cucumber Ethanolic extracts of peel

Antibacterial activity Human and food borne pathogen bacteria Serum glucose and hepatic lipid peroxidation (LPO) study in alloxan induced diabetic male mice Anti-hyperglycemic effect study by subcutaneous glucose tolerance tests on 27 healthy rabbits Hypolipidemic action in normal and cholesterol fed experimental rats Pyloric ligation and water immersion stress induce rat models Inhibited chitin oligosaccharides

[47]

[48]

1995

Fruits

[50]

Hypolipidemic activity Ulcer protective Anti-parasitic activity

1999

Pectin extracted from the fruit

[51]

2009 1979

Methanolic extract of seeds Exudates of the fruit

[53] [52]

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responsible for total antioxidant activity was calculated through total oxy-radical scavenging capacity (TOSC) assay and found to be 1.280.05 mol of vitamin C equiv/g of sample. Phenolic Antioxidant Index (PAI) 0.004 and bioactivity index (BI) 0.01 were also determined in this experiment. Sotiroudis et al., (2010) estimated the phenolic content of the methanolic extracts of three cucumber tissues, peel, pulp and juice and found that the pulp had the highest amount of phenolics (more than twofold the amount present in peel and juice) while the juice had the lowest amount [2]. They found that cucumber pulp and peel extracts contain a high concentration of lactic acid (~78% w/w). Pulp tissue contains more than 50% (59.9%) of lactic acid followed by peel (25.1%) and juice (15%), which are used for treatments of warts, xerosis and chemical peeling of the skin [40,41]. Anti-oxidant activities of cucumber ethanol and water extract were found to be 34.3 and 28.0% respectively, when this activity was determined according to -carotene bleaching method along with 36 other vegetables. The total phenolic content (TPC) was found to be 48.00.9 mg /100 g [42]. C. sativus fruit has been referred as a potential antiwrinkle agent in cosmetic products. It showed significant effect with DPPH-free radical and superoxide radical scavenging activity, IC50 at concentration of 14.73 1.42 and 35.29 1.30 g/ml, respectively. In vitro anti-hyaluronidase and anti-elastase activity, IC50 at a concentration of 20.98 1.78 and 6.14 1.74 g/ml respectively also supported the anti-wrinkle property of this plant [9]. Similar kinds of studies have been proved by Maity et al. (2011) in also in the Tagetes erecta flower [43]. The fruit extract showed a sun protective factor (SPF) value of 0.67 0.54 at a concentration of 200 g/ml of sample [44] supporting its cosmetic uses. Kai et al., (2008) studied the inhibitory effects of melanogenesis on C. sativus and found that MeOH extracts of leaves and stems inhibited melanin production in B16 cells by decreasing tyrosinase expression at the protein level [45]. The results suggested that the out of eight compounds isolated from the leaves, lutein (IC50 = 170.7 M), and (+) (1R, 2S, 5R, 6S)-2, 6-di-(4-hydroxyphenyl)-3,7dioxabicyclo [3.3.0] octane (IC50 = 270.8 M) decreased tyrosinase expression suppress melanogenesis and showed de-pigmentation activity. Kamkaen et al., (2007) studied anti-tyrosinase activity (mushroom tyrosinase inhibition) against a positive control, kojic acid on 16 tropical vegetables including C. sativus extracts [46]. Volatile oil of cucumber (cultivated in a greenhouse at Crete; South Greece) showed antibacterial activity (MIC=0.090.50 mg/mL) against Gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis and Gram-negative bacteria: Escherichia coli, Enterobacter cloacae, Klebsiella pneumonia, Pseudomonas aeruginosa; and antifungal activity (MIC=1.84 2.90 mg/mL) against human pathogen fungi: Candida albicans, Candida tropicalis and Candida glabrata. [2]. Phyto-constituents (E, Z)-2, 6-nonadienal (NDE) and (E)-2-nonenal (NE) present in cucumber showed antibacterial activity against human and food borne pathogen bacteria such as Bacillus cereu,s Escherichia coli, Listeria monocytogenes and Salmonella typhimurium [47]. Dixit and Kar [48] studied the effect of cucumber peel extract in diabetic mice to find the possible role in ameliorating diabetes mellitus along with related changes in serum lipids and hepatic lipid peroxidation (LPO). They found that 500 mg/ kg b.wt/d for 15 days dose reverses the enzyme associated

with the diabetes [48]. Cucurbitaceae plants of Indian origin including C. sativus when studied for blood sugar lowering potential at dose of 250 mg/kg by oral administration, it was found that the fruit does not affect the blood sugar level or depress the peak value, after glucose load [49], whereas another study suggested that C. sativus decreases significantly the area under the glucose tolerance curve and the hyperglycemic peak on 27 healthy rabbits [50]. The oral administration of the pectin extracted from the fruit of C.sativus at a dose of 5 g/kg body weight/day showed significant hypolipidemic action in normal as well as cholesterol-fed experimental animals [51]. Allen (1979) studied that lectin from the exudates of the fruit of the cucumber having an anti-parasitic function that strongly inhibited by chitin oligosaccharides [52]. The seeds are useful for quitting burning sensation, constipation, tonic and intermittent fevers [16]. Gill et al., (2009) suggested that the methanolic extract of C. sativus seeds possessed significant ulcer potential which could be due to the antioxidant activity at a dose of 300 mg/kg in pyloric ligation and water immersion stress induced rat models [53]. The induction effect of UV-B on the antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), ascorbic acid peroxidase (APX) and glutathione reductase (GR) and its suppressed modulation to detoxify excess ROS via external application of a-tocopherol and benzoquinone in cucumber cotyledons have also been examined [54]. Boiled leaves with cumin seeds are useful for throat infection. Powdered leaf with sugar acts as a diuretic and it is also given to treat remitted and inflammatory fevers [4]. 6. Cucumber used in cosmetic The whole range of cosmetic usage and its practice as conceived by the ancient medicinal systems was based on natural resources [55]. As folk medicines and folk cosmetics, cucumber pulp has been used to clean skin for centuries around the world. The fruits and seeds of cucumber are recommended globally to prepare cosmetic products for the treatment of various skin problems like wrinkles and sunburn [56]. The pulp of cucumbers is primarily composed of water with ascorbic acid (vitamin C) and caffeic acid, which gives a soothing effect on skin and reduces swelling. Anti-hyaluronidase and anti-elastase activity of lyophilized juice of C. sativus proved that it may have potential role on skin care [9]. The fruit pulp having natural -hydroxyacid compounds like lactic acid, is widely used in cosmetics to reduce the thickness of the stratum corneum by reducing corneocyte cohesion and used for dry skin, icthyosis, follicular hyperkeratosis, seborrheic keratosis, actinic and keratosis [2,57,58]. Pulp tissues are used for treatments of warts, xerosis and chemical peeling of the skin [40,41]. Sun Protective Factor (SPF) value 0.670.54 at concentration of 200 g/ml fruits extract supported its uses for cosmetic preparation [44]. Fresh cucumber extract contains many useful ingredients, which can help in treating so many skin problems and used as a skin caring product like face packs, facials, juice and many other product [59]. Cucurbitacin D and 23, 24-dihydrocucurbitacin D, are found in cucumber extracts and these are responsible for the inhibition of tyrosinase and melanin synthesis [60]. One major volatile compound known as trans cis-2, 6-nonadienal of cucumber was characterized as a noncompetitive inhibitor against 4-tert-butylcatechol oxidation by mushroom tyrosinase

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[61]. Hard fruit skin is rich in fiber and contains a variety of beneficial minerals including silica, potassium and magnesium, which shows a cooling effect [59] and therefore C. sativus can be used as a potential anti-wrinkle agent in cosmetic products [9]. Akhtar et al., (2011) developed a topical skin-care cream, water in oil (w/o) emulsion with 3% hydro-alcoholic extracts of cucumber and observed that the formulation decreases skin moisture and melanin content as well as increase trans-epidermal water loss (TEWL), which strengthens the anti-acne effects and acts as a whitening agent [62]. Su (2003) prepared a skin massage agent with cucumber fruit, which can supplement nutrients and water to skin, to prevent skin aging, to improve skin elasticity, and to promote skin metabolism [63]. It is also effective in the treatment of improved winkles, and do moisten the skin. Hwa (2007) prepared a massage pack containing cucumber as natural plant material for preventing skin keratin such as skin aging, and for deriving the beneficial effects to the skin along with beautification [64]. Yeong (2010), prepared a cosmetic pack by mixing minerals and extracts from mulberry and cucumber with pulverizing kaolin, sericite and muscovite, which enhances skin elasticity, minimizes skin pores, effectively removes bacteria and wastes, prevents skin aging, and has a whitening effect [65]. To prevent the formation of wrinkles and the sagging of skin, a mixture of nutrient liquids has been prepared by mixing 1000 g cucumber with aloe and other 4 plant materials [66]. Another cosmetic product has been reported, which is composed of D-panthenol, silk peptide powder, cucumber ext. and aloe ext. [67]. Lee et al. (2003) studied that transgenic cucumber fruits produce elevated level of an anti-aging superoxide dismutase approximately 3 times higher than in those of non-transgenic plants [68]. Hoon et al., (2000) made a cosmetic preparation from cucumber with other plant extracts, which is having a good antioxidant, cell-regenerating and anti-aging effect [69]. However an additional clinical trial is necessary to optimize the application of these natural ingredients for cosmetics. The scientific validation for the safety and efficacy of botanical extracts and compounds for treating aging skin is utmost necessary [70].

References
[1] Kirkbride JH. Biosystematic monograph of the genus Cucumis (Cucurbitaceae). Boone, North Carolina: Parkway Publishers; 1993. [2] Sotiroudis G, Melliou Sotiroudis E, Chinou I. Chemical analysis, antioxidant and antimicrobial activity of three Greek cucumber (Cucumis sativus) cultivars. J Food Biochem 2010;34:61-78. [3] Peter KV, Abraham Z. Biodiversity in horticultural crops. New Delhi: Daya publishing house; 2007. [4] Kapoor LD. CRC handbook of Ayurvedic medicinal plants. Florida: CRC Press LLC; 1990. [5] Mukherjee PK, Maity N, Nema NK, Sarkar BK. Bioactive compounds from natural resources against skin aging. Phytomedicine 2011;19:64-73. [6] Anonymous. Ayurvedic Pharmacopoeia of India, The Controller of Publication. New Delhi: National Institute of Science Communication and Information Resources (NISCAIR); 2001. [7] Franco P, Vittorio S, Robert A. Plants in cosmetics. Press-Council of Europe; 2002. [8] Chuyaku-Daijiten. Shanghai Technology. Tokyo: Shogakukan Press; 1985. [9] Nema NK, Maity N, Sarkar B, Mukherjee PK. Cucumis sativus fruitpotential antioxidant, anti-hyaluronidase, and anti-elastase agent. Arch Dermatol Res 2011;303:247-52. [10] Aburjai T, Natsheh FM. Plants used in cosmetics. Phytother Res 2003;17:9871000. [11] Chen JF, Staub JE, Tashiro Y, Isshiki S, Miyazaki S. Successful interspecific hybridization between Cucumis sativus L. and C. hystrix Chakr. Euphytica 1997;96:413-9. [12] Renner SS, Schaefer H, Kocyan A. Phylogenetics of Cucumis (Cucurbitaceae): cucumber (C. sativus) belongs in an Asian/Australian clade far from melon (C. melo). BMC Evol Biol 2007;7:111. [13] Whitaker TW, Davis GN. Cucurbits botany, cultivation, utilization. New York: Interscience Publication; 1996. [14] Anonymous. The wealth of India, vol. 2nd, 1st supplement series. New Delhi: National Institute of Sciences Communication and Information Resources (NISCAIR); 2010. [15] Indian Agricultural Research Institute (IARI), Department of Agricultural Research and Education, Ministry of Agriculture, Govt. of India. New Delhi, 2012, www.iari.res.in. [16] Warrier PK. Indian medicinal plants: a compendium of 500 species. Chennai: Press Orientlongman; 1994. [17] Chen JC, Chiu MH, Nie RL, Cordell GA, Qiu SX. Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep 2005;22:386-99. [18] Rice CA, Rymal KS, Chambliss OL, Johnson FA. Chromatographic and mass spectral analysis of cucurbitacins of three Cucumis sativus cultivars. J Agric Food Chem 1981;29:194-6. [19] Hideki H, Hidekazu ITO, Katsunari I, Keiko A, Yoshiteru S, Isamu I. Cucurbitacin C-bitter principle in cucumber plants. JARQ-Jpn Agric Res Q 2007;41:65-8. [20] Enslin PR, Joubert FJ, Rehm S. Bitter principles of the cucurbitaceae. III.-Elaterase, an active enzyme for the hydrolysis of bitter principle glycosides. J Sci Food Agric 1956;7:646-55. [21] Pittenger DR. California Master Gardener Handbook, Volume 3382. California: University of California. Division of Agriculture and Natural Resources Publication; 2002. [22] Barham WS. The inheritance of a bitter principle in cucumbers. Proc Am Soc Hort Sci 1953;62:441-2. [23] Peerce LK, Wehner TC. Review of gene and linkage groups in cucumber. HortScience 1990;25:605-15. [24] Kano Y, Yamabe M, Ishimoto K, Fukuda H. The occurrence of bitterness in the leaf and fruit of cucumbers (Cucumis sativus L. cv. Kagafutokyuri) in relation to their nitrogen levels. J Japan Soc Hortic Sc 1999;68:391-6. [25] Chu Y-F, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activities of common vegetables. J Agric Food Chem 2002;50:6910-6. [26] Kemp TR, Knavel DE, Stoltz LP. Identification of some volatile compounds from cucumber. J Agric Food Chem 1974;22:717-8. [27] Zhou WA, Mcfeeters RF. Volatile compounds in cucumbers fermented in low-salt conditions. J Agric Food Chem 1998;46:2117-22. [28] Peng AC, Geisman JR. Lipid and fatty acid composition of cucumbers and their changes during storage of fresh-pack pickles. J Food Sci 1976;41:859-62. [29] Garg VK, Nes WR. Occurrence of 5-sterols in plants producing predominantly 7-sterols: studies on the sterol compositions of six cucurbitaceae seeds. Phytochemistry 1986;25:2591-7. [30] Delbert DH, Baker LR, Sell HM. Isolation and identification of the gibberellins from Cucumis sativus and Cucumis melo. Planta 1972;103:241-8. [31] McNally DJ, Wurms KV, Labbe C, Quideau S, Belanger RR. Complex C-glycosyl flavonoid phytoalexins from Cucumis sativus. J Nat Prod 2003;66:1280-3.

7. Concussion The traditional and therapeutic application of C. sativus with its phytochemical profile need to be explored further based on its different activities. The phytochemical and pharmacological potential outlined throughout this review will help to maximize the desired therapeutic benefits of this well known plant species. The plant needs to be evaluated based on combined approaches of exploitation and exploration, which may help to find effective leads for further research.

Acknowledgements The authors are thankful to the Department of Science and Technology, Drug and Pharmaceutical Research Programme [DST-DPRP, File No. VI-D&P/287/08-09/TDT], Government of India, New Delhi and Parker Robinson Pvt. Ltd., Kolkata, India for financial support through DST-DPRP Programme.

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P.K. Mukherjee et al. / Fitoterapia 84 (2013) 227236 [53] Gill NS, Garg M, Bansal R, Sood S, Muthuraman A, Bali M, et al. Evaluation of antioxidant and antiulcer potential of Cucumis sativus L. seed extract in rats. Asian J Clin Nutr 2009;1:131-8. [54] Jain K, Kataria S, Guruprasad KN. Effect of UV-B radiation on antioxidant enzymes and its modulation by benzoquinone and a-tocopherol in cucumber cotyledons. Curr Sci 2004;87:87-90. [55] Mukherjee PK, Venkatesh P, Venkatesh M, Ponnusankar S, Khan Y. Strategies for revitalization of traditional medicine. Chinese Herb Med 2010;2:115. [56] James AD. The Green Pharmacy. Emmaus, Pennsylvania: Rodale Press; 1997. p. 394-459. [57] Scott EV, Yu R. Hyperkeratinization, corneocyte cohesion and alpha-hydroxy acid. J Am Acad Dermatol 1984;5:867-79. [58] Van Scott E, Yu R. Alpha-hydroxy acids: procedures for use in clinical practice. Cutis 1989;43:222-8. [59] Sumathi T, Ponnuswami V, Senthamizh BS. Anatomical changes of cucumber (Cucumis sativus L.) leaves and roots as influenced by shade and fertigation. Res J Agric Biol Sci 2008;4:630-8. [60] Jian CC, Ming C, Rui LN, Geoffrey AC, Samuel XQ. Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep 2005;22:386-99. [61] Fernando GH, Mercedes JN, Juana C, Francisco GC, Josefa E. Tyrosinase inhibitory activity of cucumber compounds: enzymes responsible for browning in cucumber. J Agric Food Chem 2003;51:7764-9. [62] Akhtar N, Mehmood A, Khan BA, Mahmood T, Muhammad H, Khan S, et al. Exploring cucumber extract for skin rejuvenation. Afr J Biotechnol 2011;10:1206-16. [63] Su CJ. A skin massage agent containing Succus Cucumidis sativi, lemon, and Eupolyphaga Seu Steleophaga juice for preventing skin aging and improving moisture retention and preparation method thereof. Repub. Korean Kongkae Taeho Kongbo; 2003CODEN: KRXXA7 KR 2003005078 A 20030115. [64] Hwa CJ. Method for preparing massage pack containing plant extracts for preventing skin keratin trouble. Repub. Korean Kongkae Taeho Kongbo; 2007CODEN: KRXXA7 KR 2007121272 A 20071227. [65] Yeong YJ. Method for preparing cosmetic pack containing minerals and extracts from mulberry and cucumber. Repub. Korean Kongkae Taeho Kongbo; 2010CODEN: KRXXA7 KR 2010026644 A 20100310. [66] Sun CW. Concentrated nutrient liquid of night cosmetic for providing anti-aging benefits and massages effect. Repub. Korean Kongkae Taeho; 2002CODEN: KRXXA7 KR 200207774 A 20021014. [67] Guizhou Z. Anti-aging cosmetics containing panthenol and silk peptides and plant extracts. Zhang Guizhou, Peop. Rep. China. Faming Zhuanli Shenqing Gongkai Shuomingshu; 2002CODEN: CNXXEV CN 1370518 A 20020925. [68] Lee HS, Kwon Eun-Jeong, Kwon Suk-Yoon, Jeong Yu-Jeong, Lee Eun-Mo, Jo Man-Hyun, et al. Transgenic cucumber fruits that produce elevated level of an anti-aging superoxide dismutase. Mol Breed 2003;11:213-20. [69] Hoon L, Sang IN, Hyeo JK, Jin SJ, Wook KB, Dong LJ. Cosmetic composition containing effective ingredients extracted from plants. Repub. Korean Kongkae Taeho Kongbo; 2000CODEN: KRXXA7 KR 2000028547 A 20000525. [70] Mukherjee PK, Ponnusankar S. Exploring pharmacovigilance for traditional herbal medicines. In: Gupta VK, editor. Comprehensive Bioactive Natural Products. USA: M/S Studium Press LLC; 2010. p. 248-80.

[32] Kai H, Baba M, Okuyama T. Two new megastigmanes from the leaves of Cucumis sativus. Chem Pharm Bull 2007;55:133-6. [33] Abou-Zaid MM, Lombardo DA, Kite GC, Grayer RJ, Veitch NC. Acylated flavone C-glycosides from Cucumis sativus. Phytochemistry 2001;58:167-72. [34] Krauze-Baranowska M, Cisowski W. Flavonoids from some species of the genus Cucumis. Biochem Syst Ecol 2001;29:321-4. [35] Guha J, Sen SP. The cucurbitacins: a review plant. Biochemistry 1975;2: 12-28. [36] Miller HE, Rigelhof F, Marquart L, Prakash A, Kanter M. Antioxidant content of whole grain breakfast cereals, fruits and vegetables. J Am Coll Nutr 2000;19:312S-9S. [37] Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr 2003;133: 2812-9. [38] Stratil P, Klejdus B, Kuban V. Determination of total content of phenolic compounds and their antioxidant activity in vegetables: evaluation of spectrophotometric methods. J Agric Food Chem 2006;54:607-16. [39] Melo EDA, Lima VLAG, Maciel MIS, Caetano ACS, Leal FLL. Polyphenol, ascorbic acid and total carotenoid contents in common fruits and vegetables. Braz J Food Technol 2006;9:89-94. [40] Wehr R, Krochmal ML, Bagatelle F, Ragsdale WA. Controlled two-centre study of lactate 12% lotion and a petrolatum-based cream in patients with xerosis. Cutis 1986;37:205-7. [41] Murad H, Shamban AT, Premo PS. The use of glycolic acid as a peeling agent. Dermatol Clin 1995;13:285-307. [42] Kaur C, Kapoor HC. Anti-oxidant activity and total phenolic content of some Asian vegetables. Int J Food Sci Technol 2002;37:153-61. [43] Maity N, Nema NK, Abedy MdK, Sarkar BK, Mukherjee PK. Exploring Tagetes erecta Linn flower for the elastase, hyaluronidase and MMP-1 inhibitory activity. J Ethnopharmacol 2011;137:1300-5. [44] Hogade MG, Patil BS, Prashant D. Comperitive sun protection factor determination of fresh fruit extract of Cuccumber vs marketed cosmetic formulation. Res Pharm Biol Chem Sci 2010;1:55-9. [45] Kai H, Baba M, Okuyama T. Inhibitory effect of Cucumis sativus on melanin production in melanoma B16 cells by downregulation of tyrosinase expression. Planta Med 2008;74:1785-8. [46] Kamkaen N, Mulsri N, Treesak C. Screening of some tropical vegetables for anti-tyrosinase activity. Thai Pharm Health Sci J 2007;2:15-9. [47] Cho MJ, Buescher RW, Johnson M, Janes M. Inactivation of pathogenic bacteria by cucumber volatiles (E, Z)-2, 6- nonadienal and (E)-2-nonenal. J Food Prot 2004;67:1014-6. [48] Dixit Y, Kar A. Protective role of three vegetable peels in alloxan induced diabetes mellitus in male mice. Plant Foods Hum Nutr 2010;65:284-9. [49] Chandrasekar B, Mukherjee B, Mukherjee SK. Blood sugar lowering potentiality of selected Cucurbitaceae plants of Indian origin. Indian J Med Res 1989;90:300-5. [50] Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol 1995;48:25-32. [51] Sudheesh S, Vijayalakshmi NR. Lipid-lowering action of pectin from Cucumis sativus. Food Chem 1999;67:281-6. [52] Allen AK. A lectin from the exudate of the fruit of the vegetable marrow (Cucurbita pepo) that has a specificity for beta-1, 4-linked N-acetylglucosamine oligosaccharides. Biochem J 1979;183:133-7.