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IJGHC; 2012, Vol.1.No.1, 61-74.

E- ISSN: 2278 3229

International Journal of Green and Herbal Chemistry


Available online at www.ijghc.org
HERBAL CHEMISTRY
Research Article

Anti ageing drugs in Ayurveda


Charmi S. Mehta and Vimal R. Joshi
2

Department of RS &BK, J.S Ayurved College, Nadiad (Gujarat) INDIA Department. of Rasashastra and Bhaishjya Kalpana, J.S Ayurved College, Nadiad (Gujarat) INDIA

Received: 16 April 2012; Revised: 24 April 2012; Accepted: 29 April 2012

ABSTRACTS
Ageing (British English) or aging (American English) is the accumulation of changes in a person over time. Ageing in humans refers to a multidimensional process of physical, psychological, and social change .Anti ageingisthetermusedtoslowerdowntheprocessofageinginthecellsofthebody.Thisconceptisdescribed under a separate section in Ayurved known as Rasayana Chikitsa. Various procedures and herbs having anti ageing properties are described. Also separate groups of herbs having ant ageing properties are described under the section of Vayahsthapana gana, Jeevaniya gana etc. Drugs like Ashwagandha, Tulsi, Haridra, Guduchi,Amalakietchavebeenprovenfortheirantageingeffectbyvariousresearches

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Keywords: Keywords: Ageing, Rasayana, anti ageing, antioxidants.

INTRODUCTION
Ageing is defined as gradual biological impairment of normal functions, probably as a result of changes made into the cells and structural components. These changes would consequently have a direct impact on functional ability of organs and biological symptoms1. Ayurved counters the aging and its allied ill-effects with three pronged approach. First it recommends the countering of aging and its adverse effects by use of Vayasthapak drugs (age stabilizers) and the second approach is to rejuvenate the aged body by Jeevneeya drugs (vitalisers) and the third approach is Jarachikitsa i.e. Rasayana Chikitsa. (rejuvenating process and formulations). Life extension science, also known as anti-aging medicine, experimental gerontology, and biomedical gerontology, is the study of slowing down or reversing the processes of aging to extend both the maximum and average lifespan2 The theme of World Health Day 2012, marked on 7 April 2012, is devoted to "Ageing and continuing good Health3". Jara (ageing) is divided in Ayurveda as Swabhavika Vyadhi (natural disease) while premature ageing can surely be reversed by Ayurvedic treatment. Even normal ageing can be slowed down by ant ageing herbs of Ayurveda. Experimental studies done on various rasayana drugs prove that they have immune stimulant, antioxidant, and antistress etc properties.

CONCEPTUAL STUDY
Rasayana is the therapy, which establishes the age (Vayasthapana), increases the life span (Ayuskar), intelligence (Medha) and strength (Bala) as well as it enables the person to rid of the diseases4 61 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

Anti ageing. Anti ageing drugs described in Ayurved are divided into a group i.e (a)Vayasthapak gana (Age stabilizer drugs) 5 These herbs are listed below. 1. Guduchi- Tinospora cordifolia . 2. Haritiki. Terminalia chebula. 3. Amalki. Emblica officinale. 4. Yukta. Pluchea lanceolata. 5. Shweta. Clitoria ternatea. 6. Jeewanti. Leptadenia reticulata . 7. Atirasa. Asperagus racemosus. 8. Mandookparni. Centella asiatica. 9. Sthira. Desmodium giganticum . 10. Punarnava. Boerhaavia diffusa .

Charmi S. Mehta and Vimal R. Joshi.

Among all, Amalaki is considered as best vayasthapana by Acharya Charaka6. These drugs may possess agesustaining and health promotive properties. Amalaki is also considered as the best rasayana drug by vrundmahava-39-19. Acharya Charaka has also described Jeevaniya Mahakashaya which contains drugs like Jeevak, Yashtimadhu, jeevanti etc along with Balya Mahakashaya which possess drugs like Ashwagandha, Shatavari, bala etc7. Both of these Mahakashayas have health promoting quality and can help in the prevention and management of aging. Rasayana is a therapy which is to be used according to different decades. Likewise, many herbs have been described to be used as per the age as follows-

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Table- 1: Rasayana herbs used according to age8 Life Decade 01 10 11 20 21 30 31 40 41 50 51 60 61 70 71 80 81 90 91 100 Desired effect Childhood (Balya) Growth (Vriddhi) Complexion (Prabha) Intellect (Medha) Skin (Twak) Vision (Drishti) Reproduction (Shukra) Vilour (Virya) Reasoning (Buddhi) Motororgans (Karmendriya) Suitable Rasayana Vacha (Acorus calamus) Ashwagandha (Withania somnifera), Bala (Sida cordifolia) Amalaki (Emblica officinalis) Shankhapushpi (Convolulus pluricaulis), Jyotishmati (Celastrus panniculatus) Bhringaraja (Eclipta alba), Tuvaraka (Hydnocarpus laurifolia) Chakshushya ( Cassia absus) Kapikachhu,(Mucuna prurita) Ashwagandha (Withania somnifera) Amalaki (Emblica officinalis), Bala (Sida cordifolia) Brahmi (Bacopa monnieri ) Bala (Sida cordifolia)

Curative rasayana are also described for management of diseases particularly in old age because they act dually as rasayana and disease pacifier and helps to regain health easily in elderly patients. 62 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

Anti ageing.

Charmi S. Mehta and Vimal R. Joshi. Table-2: Rasayana herbs used for various diseases9

Disease Eye Heart Skin Tuberculosis Anemia Asthma Neuropathies Diabetes Lipid disorders Hypertension Psychosis

Suitable Drugs Jyotishmati, Triphala, Shatavari, Yashtimadhu Shalaparni, Arjuna, Guggulu, Pushkaramula Tuvaraka, Bhallataka, Vidanga, Somaraji Rasona, Nagabala, Shilajit, Pippali Makshika, amalaki Agatsya Rasayana, Bhallataka, Shirisha, Haridra Rasona, Guggulu, Bala, Nagabala Shilajatu, Amalaki, Haridra, Guduchi, Jambu, Methika Guggulu, Haritaki, Pushkaramula, Vacha Rasona, Bala, Rasna, Sarpagandha, Ashwagandha Shankhapushpi, Brahmi, Mandukaparni

Likewise, various formulations are also given which posses ant ageing property like-Chyavanprashaavleha-In the present time, this is the most famous Rasayana formulation. This may be a product named after the patient (Rishi Chwayan for whom Ashwini Kumar created this product.) It contains anti aging, strengthening, aphrodisiac and vitalizer herbs10. Likewise, Amalaki rasayana, Bhallataka rasayana, Triphala Rasayana, Vardhman Pippali Rasayana etc are various formulations which posses ant ageing property and can also be used in various diseases.

DISCUSSION

Out of the 8 branches of Ayurved- Rasayana/ jarachikitsa is devoted to cure aging and its ill effects. From the rasayana treatment, one attains longevity, memory, intelligence, freedom from disorders, youthful age, excellence of luster, complexion and voice, oratory, optimum strength of physique and sense organs, respectability and brilliance. It means the attaining the excellent Rasa etc.11 Types of Rasayana: (a).Kutipraveshika12 Indoor: A special cottage is built on a auspicious ground, in the neighbourhood of holy people and where all conveniences are available. It has three rooms one after another, all-weather worthy. It must be sound proof. (b).Vatatapika13 Open air: This method is outdoor method. (c).Kamya Rasayans14 (use oriented) 1. Medhya Rasayan: Promote intelligence Specific formulation is prescribed. 2. Prana Rasayan: Promote age-stablization, longevity and vitality- Most formulations are in this category. 3. Srikamya Rasayan: Promote complexion Specific formulations are prescribed. Rasayanas based on drug, diet and life style: 1. Aushdha Rasayana - Drug Based Rasayana. 2. Ahara Rasayana - Dietary Rasayana. 3. Achara Rasayana - Lifestyle Rasayana. 63 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

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Anti ageing. (d).Naimittika Rasayans help to fight a specific disease.

Charmi S. Mehta and Vimal R. Joshi.

Presently considerable research is being carried out on various Rasayana Products and the herbs to screen them for various therapeutic benefits. But the research is focusing only one or couple of aspects of Rasayans therapeutic benefits. The exhaustive research on all therapeutic benefits of single Rasayana product will be more conclusive validation of claims of classical Ayurvedic texts15. Various studies are done on different aspects of Rasayana drugs can some contemporary terminologies are found which have actions similar to Rasayana like Immunomodulator Adaptogenic Antioxidant Nootropic Antistress

These terms can be understood as followsImmunomodulator- a substance that alters the immune response by augmenting or reducing the ability of the immune system to produce antibodies or sensitized cells that recognize and react with the antigen that initiated their production16. Several medicinal plants used in the Indian traditional system known as Rasayana (devoted to enhancement of the bodys resistance) have attracted the attention of scientists world-wide. As discussed below, several medicinal plants exhibit not only immunomodulatory activity but also a wide range of antioxidant, antiasthmatic, antiarrhythmic, anti-inflammatory, hepatoprotective, hypocholesterolemic, antifungal, cardiotonic, diuretic, and other medicinal activities17.

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CLASSIFICATION OF IMMUNOMODULATORS
Clinically, immunomodulators can be classified into the following three categories: Immunoadjuvants: are used to enhance the efficacy of vaccines and therefore could be considered specific immune stimulants. Immunoadjuvants hold the promise of being the true modulators of the immune response. It has been proposed that they be exploited as selectors between cellular and humoral helper T1 (Th1) and helper T2 cells (Th2), immunoprotective, immunodestructive, and reagenic [immunoglobulin E (IgE)] versus IgG type immune responsesposing a real challenge to vaccine designers18. Immunostimulants: are inherently non-specific as they are envisaged as enhancements to a bodys resistance to infection. They can act through innate as well as adaptive immune responses. In healthy individuals, the immunostimulants are expected to serve as prophylactic and promoter agents, i.e., as immunopotentiators, by enhancing the basic level of immune response. In the individual with impairment of immune response, they are expected to act as immunotherapeutic agents19. Immunosuppressants: are a structurally and functionally heterogeneous group of drugs, which are often concomitantly administered in combination regimens to treat various types of organ transplant rejection and autoimmune diseases20.

64 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

Anti ageing.

Charmi S. Mehta and Vimal R. Joshi. Table 3: A brief description of common plant-derived immune modulators

Botanical (Family)

Ayurvedic/ Part Common name used Tulasi Entire plant

Chemical constituents Essential oils such as eugenol, cavacrol, derivatives of ursolic acid, apigenin Anthraquinone glycosides

Other biological activities Carminative, stomachic, antispasmodic, antiasthmatic, hepatoprotective21-24

Ocimumsanctum Linn. (Labiateae)

Aloe vera Tourn.ex Linn. (Liliaceae)

Kumaari

Gel from leaves

Purgative, emmenagogue, emollient, anti inflammatory 25,26. Hepatoprotective, antispasmodic, blood purifier, febrifuge27

Andrographis paniculata Nees (Acanthaceae)

Kaalmegha

Leaves

Diterpenes

Asparagus racemosusWild. (Liliaceae)

Shatavaari

Roots

Tinospora cordifoliaMiers. (Menispermiaceae)

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Amrita, guduuchii Entire herb Alkaloidal constituents such as berberine, tinosporic acid Flavonoids, oligomeric proanthocyanidins, tannins Flavonoids, betasitosterol, lupeol Arjuna Leaves, bark Cardiotonic, diuretic, prescribed for hypertension30. Kaanchanar Roots, bark, buds Roots, flowers Leaves Antifungal, astringent 31 . Naagabala Flavanoids Diuretic, emollient, antispasmodic32. Antidiabetic, diuretic, antibilious33. Antioxidant34.

Saponins, sitosterols Ulcer healing agent, nervine tonic, antigout28

Hypoglycaemic agent, antipyretic29.

Terminalia arjuna Roxb. (Combretaceae )

Bauhinia variegata Linn. (Caesalpiniaceae)

Urena lobata Linn. (Malvaceae)

Gymnema sylvestre R.Br. (Asclepiadaceae) Picrorhiza scrophulariiflora Benth. (Scrophulariaceae)

Gambhari

Sapogenins

Kutki

Roots

Iridoid glycosides, amphicoside

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Anti ageing. Botanical (Family) Ayurvedic/ Part Common name used Atibalaa Whole plant Leaf, seeds Leaf

Charmi S. Mehta and Vimal R. Joshi. Chemical constituents Flavonoids, triterpenoids Iridoid glucosides Other biological activities Diuretic, antibacterial35. Anti-inflammatory, antispasmodic36. Hypoglycaemic, astringent37. Hypoglycaemic38. Immunostimulatory39. Immunomodulator40.

Abutilonindicum linn. (Malvaceae)

Nyctanthesarbor-tristisL. (Oleaceae) Acaciacatechu Willd. (Leguminosae) Boswellia spp. (Burseraceae)

Paarijaata

Khadira

Flavonoids, quercetin Triterpenes, ursanes

Shallaki

Gum resin Herb Herb

Boerhaavia diffusa(Nyctaginaceae) Centella asiatica Linn. (Umbelliferae), Eclipta alba L. (Compositae)

Punarnava Brahmi

Alkaloid Triterpenoid saponins Triterpenoid glucoside

Bringraja

Leaves

Convolvulus pluricalis Linn. (Convolvulaceae)

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Shankhpushpi Herb Alkaloids Brain tonic42. Sahijan Leaves Vitamin A, B, C, carotenoids, saponins Alkaloids Antioxidant43. Pipali Fruits Antioxidant44.

Anticancer, antileprotic, analgesic, antioxidant, antimyotoxic41.

Moringa oleifera L. (Moringaceae)

Piper longum L. (Piperaceae)

MECHANISM OF ACTION OF THE RASAYANAS/IMMUNE MODULATORS45 It has been reported that the Rasayanas are rejuvenators, nutritional supplements and possess strong antioxidant activities. They also exert antagonistic action on oxidative stressors, giving rise to the formation of different free radicals. They are used mainly to combat the effects of ageing, atherosclerosis, cancer, diabetes, rheumatoid arthritis, autoimmune disease and Parkinsons disease. The Rasayana herbs seem to operate through immunostimulant, immunoadjuvant, and immunosuppressant activities or by affecting the effector arm of the immune response.11 Mechanisms of immunomodulation activity occur mainly via phagocytosis stimulation, macrophages activation, immunostimulatory effect on peritoneal macrophages, lymphoid cells stimulation, cellular immune function enhancement and nonspecific cellular immune system effect, antigen-specific immunoglobulin production increase, increased nonspecific immunity mediators and natural killer cell numbers, reducing chemotherapy-induced leukopenia, and increasing circulating total white cell counts and interleukin-2 levels 66 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

Anti ageing.

Charmi S. Mehta and Vimal R. Joshi.

Table-4: Pharmacology of immunomodulatory activities from putative medicinal plants


Plant/Family name Dose administere d 200 mg/kg p.o. Type of solvent extract Aqueous/alcoholi c In vitro/in vivomode l HA titer Mechanism involved and observation Extract shows increased DTH to sheep red blood cells SRBCs. Alcoholic extract was more potent than aqueous in producing delayed type hypersensitivity response. Both extracts have marginal stimulatory effect on humoral immunity46. Acemannan (primary polysaccharide from Aloe vera gel) incubated on special type of mouse macrophage cell line, RAW 264.7 for 24 h causes immunostimulation due to activation of macrophages47-49. Andrographolide acts as inhibitor of TNF- and induces significant stimulation of both antigen specific and antigen nonspecific types of immune responses in mice, showing effectiveness against a variety of infectious and oncogenic (cancer causing) agents50. Aqueous extract showed immunoadjuvant effect on experimental animals when immunized with diphtheria, tetanus, and pertussis vaccine. Reduced mortality coupled with overall improved health status was observed in treated animals, indicating the development of a protective immune response51. Improves the phagocyte function without affecting cell-mediated and humoral immune systems and also causes inhibition of

Ocimum sanctumLinn. (Labiateae)

Aloe vera Tourn.ex Linn. (Liliaceae)

100 g/mL

Hydrogel

Mouse macrophage cell line, RAW 264.7

Andrographis paniculata Nees (Acanthaceae)

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Dose dependent Alcoholic Mitogen induced lymphocyte proliferation 100 mg/kg body weight Aqueous HA titer

Asparagus racemosus Wild. (Liliaceae)

Tinospora cordifolia Miers. (Menispermiaceae)

p.o.

Aqueous, methanolic

In vitro phagocytic activity, HA titer, hypersensitivity response, inhibition of allogenic

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Anti ageing. Plant/Family name Dose administere d Type of solvent extract

Charmi S. Mehta and Vimal R. Joshi. In vitro/in vivomode l transplant rejection Mechanism involved and observation C3 canvertase of the classical complement pathway, hence acts as immunomodulator52. Plant showed immunomodulation by increasing the secondary immune response as evidenced by an increase in Anti- SRBC antibody titre (ASRBs) antibody titer but failed to modulate primary immune response53. Increase in macrophage stimulatory activity, neutrophil adhesion and hemagglutination antibody titer confirms its immunomodulatory potential54.

Terminalia arjunaRoxb. (Combretaceae)

400 mg/kg, p.o.

Aqueous, alcoholic

HA titer

Bauhinia variegataLinn. (Caesalpiniaceae)

250 500 mg/kg, p.o.

Ethanolic

Carbon clearance test and neutrophil adhesion test, HA titer

Urena lobata Linn. (Malvaceae)

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5100 g/mL Methanolic Phagocytic activity, 25 g/mL, 50 g/mL and 100 g/mL Aqueous Neutrophil locomotion and chemotaxis test, phagocytosis of killed Candida albicans and nitroblue terazolium tests HA titer, DTH Extract showed significant immunomodulation at all concentrations in various in vitro models by exerting a stimulating effect on phagocytic activity, neutrophil locomotion and chemotaxis56. 75 mg/kg, p.o. Aqueous, ethanolic

Extract showed immunostimulation in vitro an d increased phagocytic activity thus increases in phagocytic index55.

Gymnema sylvestre R.Br. (Asclepiadaceae)

Cissampelos pareira Linn. (Menispermiaceae)

Stimulates immune system, affects humoral immunity as shown by its effect in the indirect hemagglutination test, serum immunoglobulin levels. It also affects cell-mediated immunity57. Stimulates immune system, affects humoral immunity as shown by its effect in the indirect hemagglutination test, serum immunoglobulin levels.

Abutilon indicumlinn. (Malvaceae)

200, 400 mg/kg

Aqueous, ethanolic

HA titer, DTH, neutrophil adhesion test and carbon clearance test

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Anti ageing. Plant/Family name Dose administere d Type of solvent extract

Charmi S. Mehta and Vimal R. Joshi. In vitro/in vivomode l Mechanism involved and observation Also affects cell-mediated immunity, showing significant increase in neutrophil adhesion and carbon clearance58.

Acacia catechu(Leguminosae )

5 mg/kg and 50 mg/kg, p.o.

Aqueous

Neutrophil adhesion test, mice lethality test, carbon clearance assay, cyclophosphamide induced neutropenia, serum immunoglobulin levels and the hamagglutination test

Aqueous extract affects humoral immunity as shown by its effect in the indirect hemagglutination test, serum immunoglobulin levels and mice lethality test. It also has effect on the cell-mediated immunity, showing significant increase in the neutrophil adhesion, carbon clearance and a reduction in cyclophosphamide induced neutropenia59. Stimulatory effect on lymphocyte proliferation60.

Boswellia spp. (Burseraceae)

DTH = delayed type hypersensitivity response; HA = hemagglutination; IFN- = interferon-; i.p. = intraperitoneal injection; NK = natural killer; NO = nitric oxide; PMN = polymorphonuclear; p.o. = per ossa; SRBC = sheep red blood cells; TNF- = tumor necrosis factor-.

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100 L/mL

Oil

Lymphocyte proliferation assay

Adaptogen An adaptogen is a metabolic regulator which increases the ability of an organism to adapt to environmental factors, and to avoid damage from such factors. Environmental factors can be either physiological (external), such as injury or aging, or psychological(internal), such as anxiety61.Some adaptogenic herbs- are Ashwagandha, Tulsi, haridra, Pippali,Amalaki, Guduchi, shatavari etc Research studies on various drugs: Ashwaganda (Withania somnifera) is often called Indian ginseng, seemingly to group it with the ginsengs because of its similar actions. Though unrelated to other ginsengs, it appears to share their many properties and actions. Considered a tonic, an alternative, an astringent, a nervine and a sedative, 62 ashwaganda has been used in Ayurvedic medicine for more than 2,500 years. Recent studies show ashwaganda to be immuno-modulating and to aid in cases of anxiety and other psychological complaints63-65. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects 69 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

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of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defense mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation66. Antioxidant- Antioxidants are defined as 'substances whose presence in relatively low concentrations significantly inhibits the rate of oxidation of targets'. Being present in serum, these antioxidants circumvent the damage caused by oxygen free radical67. Nootropic- they are substances which promote intelligence and functions of brain. These drugs can be categorized as Medhya Rasayana drugs . Acharya Charaka has described four important medhya Rasayana drugs namely- Mandookparni, Guduchi, Yashtimadhu and Shankhpushpi68.

CONCLUSION
A separate branch of Ayurved called Rasayana Chikitsa/ jara Chikitsa have been described in Ayurved for their ant ageing effects. Under this section various herbs are described like Amalaki, guduchi, Shankhpushpi, Ashwagandha , etc. Various research studies on these plants prove their immunomodulatory, adaptogenic, nootropic etc effects which justify that various drugs used in Ayurved posses ant ageing effects

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*Correspondence Author: Charmi S. Mehta,Vimal R. Joshi; Department of RS &BK, J.S Ayurved College, Nadiad (Gujarat) INDIA; Department. of Rasashastra and Bhaishjya Kalpana, J.S Ayurved College, Nadiad (Gujarat) INDIA

74 IJGHC; Herbal Chem.; 2012, Vol.1, No.1, 61-74.

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