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Monograph: Ashwagandha

Monograph: Ashwagandha Monograph: Ashwagandha

Ashwagandha (Withania somnifera, synonym Physalis somnifera) is a small evergreen shrub that grows to about four to five feet tall. It is found in dry areas of India and the Middle East, as well as parts of Africa. The word ashwagandha means “odor of the horse” due to its distinctive smell. Ashwagandha has been used in ayurvedic medicine in India for hundreds of years. It has been used as an “adaptogenic” herb (rasayana), meaning that it is used with the intention to help the body resist physiological and psychological stress. It is purported to tone and normalize (revitalize) bodily functions. The berries may be used to coagulate milk in making cheese.

History

Orally, ashwagandha is used for arthritis, anxiety, insomnia, tumors, tuberculosis and chronic liver disease. Ashwagandha is also used as an “adaptogen” to increase resistance to environmental stress and as a general tonic. It is also used orally for immunomodulatory effects, improving cognitive function, decreasing inflammation, preventing the effects of aging, emaciation, infertility in men and women, menstrual disorders, fibromyalgia and hiccups. It is also used orally as an aphrodisiac and emmenagogue, and for treating asthma, leukoderma, bronchitis, backache and arthritis.

Topically, ashwagandha is used for treating ulcerations, backache and hemiplegia.

Safety

Ashwagandha is possibly safe when used orally and appropriately, short-term. Ashwagandha has been safely used in clinical trials lasting up to 12 weeks. Pregnancy
Ashwagandha is likely unsafe when used orally. Ashwagandha has abortifacient effects.

Effectiveness

Anxiety. In a preliminary clinical trial, subjects with moderate-to-severe anxiety received dietary counseling, deep breathing exercise instruction, a multivitamin and ashwagandha root 300 mg twice daily for 12 weeks. Anxiety scores decreased in the ashwagandha group compared to a control group receiving psychotherapy, breathing exercise instruction, and placebo. The impact of ashwagandha alone is unclear.

Attention deficit-hyperactivity disorder (ADHD). In a preliminary clinical trial, children with ADHD were given a combination herbal product, including ashwagandha or placebo for four months. Measures of attention, cognition and impulse control improved significantly in children receiving ashwagandha complared to placebo. The dose of ashwagandha in the combination product was not reported, and the effect of ashwagandha alone in ADHD is unclear.

Cerebellar ataxia. A small, open-label study evaluating ashwagandha 500 mg three times daily in combination with ayurvedic therapy for one month showed improvement in balance indices in subjects with cerebellar ataxia. The effect of ashwagandha alone is not known.

Diabetes. A case series, including six subjects with type 2 diabetes, showed that ashwagandha 3 grams daily for 30 days decreased blood glucose to a degree similar to oral hypoglycemic drugs; however, it wasn’t specifically compared to oral hypoglycemic drugs.

Hypercholesterolemia. A case series, including six subjects with hypercholesterolemia showed that ashwagandha 3 grams daily for 30 days decreased serum cholesterol, triglycerides, low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL).

Infertility. Ashwagandha root powder 5 grams daily given with milk for three months decreased oxidative stress and improved indicators of semen quality, including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin levels in a clinical trial of 150 infertile Indian males. However, sperm count and motility were largely unchanged.

Osteoarthritis. In a preliminary study, patients with joint deformity, pain, stiffness, and swelling were given a specific combination supplement, containing ashwagandha 450 mg, ayurvedic zinc complex 50 mg, guggul 100 mg and turmeric 50 mg (Articulin-F) two capsules three times daily for three months. Although symptoms were reduced, there were no radiological improvements after treatment. The effects of ashwagandha alone in osteoarthritis are unknown. Parkinson’s disease. In a preliminary study, symptom improvement was noted in 13 Parkinson’s patients who took a combination herbal product, containing ashwagandha, cowhage, Hyoscyamus reticulantus and Sida cordifolia. The impact of ashwagandha alone in Parkinson’s disease is unclear.

More evidence is needed to rate ashwagandha for these uses.

Dosing & Administration

• Adult Oral:

General: According to secondary sources, 1-6 g daily of the whole herb has been used in capsule form. 3 g of powder taken twice daily in boiled warm milk has been used. A tea has been made by simmering or boiling one part root in 10 parts water for 15-30 minutes and ingesting twice daily in the amount of 1/2 to 1-oz. at a time. Some sources have suggested 1-6 g daily of the whole herb in tea form. Tinctures or fluid extracts have been dosed at 2-4 mL, taken three times daily; this may contain high concentrations of ethanol. Five teaspoons of dried herb in one cup of boiling liquid, taken as 2-4 cups daily with raw sugar or honey, has been used.

Diabetes (type 2): Powdered roots of ashwagandha (dose and frequency unknown) have been used for 30 days.

Diuretic: Powdered roots of ashwagandha (dose and frequency unknown) have been used for 30 days.

Longevity/antiaging: Powdered ashwagandha root has been used in tablet form (0.5g), two tablets, three times daily with milk.

Children Oral:

Childhood growth promotion: 2 g of ashwagandha daily in milk has been used for 60 days with a lack of toxicity.

• Standardization
• According to secondary sources, tablets may be standardized to 4.5 mg of withanolides.

Adverse Effects

General: There are few reports of adverse effects associated with ashwagandha, and some studies did not report the doses, standardization or preparations used. One Indian trial reported treatment of 101 males with tablets totaling 3 g daily, given by mouth with milk for one year, with no serious adverse effects. In a case series, no adverse effects were noted in 12 patients treated with powdered ashwagandha root for 30 days. No toxicity was noted in 13 children treated with ashwagandha 2 g by mouth daily for 60 days.

• Cardiovascular
• Dermatologic
• Endocrine
• Gastrointestinal
• Genitourinary
• Hematologic
• Neurologic/CNS
• Psychiatric
• Pulmonary/Respiratory
• Renal
• Other

Toxicology

• Animal Data: In mice, doses of 1,000 mg/kg produced fatalities, while 500-750 mg/kg given to total cumulative doses of 7.5-10 g appeared safe. The intraperitoneal LD50 in rats has been reported as 465 mg/kg and as 432 mg/kg in mice. Subacute toxicity studies in rats did not reveal any toxicity.

• Human Data: One Indian trial reported treatment of 101 males with tablets totaling 3 g daily, given by mouth with milk for one year, with no serious adverse effects. No adverse effects were noted in 12 patients treated with powdered ashwagandha root for 30 days. No toxicity was noted in 13 children treated with 2 g of ashwagandha by mouth daily for 60 days. In a case report, a man taking “ashwagandha/mucuna” for two months experienced hemolytic anemia and abdominal pain. Lead (7.3 mg per pill), arsenic, chromium and mercury were discovered in the “ashwagandha/mucuna” supplements. Dimercaptosuccinic acid (DMSA), a heavy metal chelator, was used (30 mg/kg of body weight daily for five days, then 20 mg/kg for 14 days), successfully lowering blood lead levels.

Interactions

Interactions With Drugs

• There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia.

• Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure. Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

• Theoretically, ashwagandha might increase the effects of benzodiazepines. There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin). This may also occur with other benzodiazepines, such as alprazolam (Xanax), flurazepam (Dalmane), lorazepam (Ativan) and midazolam (Versed).

Interactions With Herbs & Supplements

Animal research suggests that ashwagandha might lower blood pressure. Theoretically, combining ashwagandha with other herbs and supplements with hypotensive effects might increase the risk of hypotension. Some of these herbs and supplements include, andrographis, casein peptides, cat’s claw, coenzyme Q10, fish oil, L-arginine, lyceum, stinging nettle, theanine, among others.

Theoretically, concomitant use with herbs that have sedative properties might enhance therapeutic and adverse effects. Some of these include, 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John’s wort, skullcap, valerian, yerba mansa, among others.

Interactions With Foods

None known. Interactions with Lab Tests

Ashwagandha contains withaferin A, which has a similar structure to digoxin. Ashwagandha can falsely elevate digoxin levels when using fluorescence polarization immunoassays (FPIA), microparticle enzyme immunoassays (MEIA) or the Abbott Digoxin III assay. The Beckman assay for digoxin seems to be only minimally affected. The Roche Tina-Quant turbidimetric inhibition immunoassay is only affected by very high ashwagandha levels, equivalent to plasma levels after an overdose.

There is some evidence that ashwagandha can stimulate thyroid hormone synthesis or secretion. Theoretically, ashwagandha might suppress thyroid stimulating hormone, (TSH) increase triiodothyronine (T3) or thyroxine (T4) values.

Interactions With Diseases

Ashwagandha might have immunostimulant effects. Theoretically, ashwagandha might exacerbate autoimmune diseases by stimulating immune activity. Advise patients with autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or others to avoid, or use ashwagandha with caution.
Ashwagandha might lower blood glucose levels. Theoretically, ashwagandha should be used cautiously in patients with diabetes as it may increase the risk for hypoglycemia in patients on insulin or oral hypoglycemic medications. Animal research shows that ashwagandha might lower diastolic and systolic blood pressure. Theoretically, ashwagandha might increase the risk of hypotension in people taking antihypertensive drugs. Advise patients taking antihypertensive medications to use ashwagandha with caution.

Animal research shows that ashwagandha might lower diastolic and systolic blood pressure. Theoretically, ashwagandha might increase the risk of hypotension in people with low blood pressure.

Theoretically, ashwagandha should be avoided by people with peptic ulcer disease because of its irritant effect on the gastrointestinal (GI) tract.

Ashwagandha has CNS depressant effects. Theoretically, ashwagandha might cause additive CNS depression when combined with anesthesia and other medications during and after surgical procedures. Tell patients to discontinue ashwagandha at least two weeks before elective surgical procedures.

There is some evidence that ashwagandha can stimulate thyroid hormone synthesis or secretion. Theoretically, ashwagandha might exacerbate hyperthyroidism as it might increase thyroid hormone levels. Ashwagandha should be used cautiously in people with hyperthyroidism or in those being treated with thyroid hormones.

Mechanism of Action

• Constituents: Constituents of ashwagandha, which have been suggested to possess biological activity include alkaloids and steroidal lactones that together are called withanolides. Numerous medicinal properties of ashwagandha have been attributed to the constituent withaferin A, and it has been suggested that longer maturation time for plants may be required for the production of withaferin A. Withanone and withanosides are also present.

• Anti-inflammatory effects: Withaferin A purportedly exerts anti-inflammatory effects. Further information is lacking.

• Anticancer effects: Withanolides are secondary metabolites from steroid oxidation and protect plants from herbivores. Ashwagandha alcoholic leaf extract, which contains withanolides, selectively demonstrated cytotoxic effects against cancer cells. Furthermore, the two closely related purified phytochemicals, in vivo and in vitro, withanolide A (Wi-A) and withanolide N (Wi-N), demonstrated differential binding effects in (normal and cancer) human cells. These findings were validated by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. Wi-A bound strongly, while Wi-N bound weakly, the latter demonstrating milder cytotoxicity toward cancer cells. It was purportedly safe for normal cells.

• Anticoagulant effects: Ashwagandha has been reported to significantly increase coagulation time in rats, although the significance in humans is unclear.

• Antidiabetic effects: According to limited human research (in patients with type 2 diabetes), ashwagandha may lower blood sugar levels and therefore may interact with diabetic medications, although the mechanism is unknown.

• Antifungal effects: In a controlled animal experiment, ashwagandha prevented the development of aspergillosis. Ashwagandha has been reported to have a protective effect on the liver and kidney of rats with carbendazim fungicide lesions.

• Antilipemic effects: In a case series, ashwagandha significantly decreased serum total cholesterol levels, triglycerides, low-density lipoprotein (LDL), and very-low-density lipoproteins (VLDL).

• Antioxidant effects: Ashwagandha has been reported to possess antioxidant properties, including prevention of lipid peroxidation in animal studies.

• Antitumor/radiosensitizing effects: Alcoholic extracts of ashwagandha dried roots, as well as the ashwagandha constituent withaferin A, have been suggested to possess antitumor or radiosensitizing properties, according to in vitro research, as well as animal research in mice and rats. Antiangiogenic properties have been reported recently. In vitro, withaferin A dose-dependently induced apoptosis in Panc-1 cells and inhibited Hsp90 chaperone activity. WA-biotin bound to the Hsp90 C-terminus, and unlabeled WA competitively blocked it. Withaferin A disrupted Hsp90-Cdc37 complexes but did not block ATP to Hsp90 binding and did not change Hsp90-P23 association. Withaferin A dose-dependently inhibited tumor proliferation in pancreatic Panc-1 xenografts.

• Cardiovascular effects: In animal experiments, ashwagandha decreased blood pressure in dogs, possessed myocardial depressant effects in rabbits, showed mild positive inotropic and chronotropic effects in frogs, and produced bradycardia in rats. Smooth muscle relaxant properties have been found. Bradycardia has been reported in rats. Ashwagandha has been associated with anticholinesterase activity, which theoretically may lead to decreases in blood pressure.

• Central nervous system (CNS) effects: Central nervous system depressant properties have been reported in animal studies, as well as interactions with sedatives such as barbiturates, ethanol and urethane. However, inhibition of morphine tolerance has also been noted in a small animal study.

In clinical research, circulating monoamine oxidase and GABA levels have been found to increase, while glutamic acid and 5-hydroxytryptophan levels decreased following 12 weeks of ashwagandha therapy.

In a functional assay using spinal cord neurons, ashwagandha demonstrated GABA-like properties and enhanced diazepam effects in animals. Ashwagandha has also been suggested to posses antidepressant effects, according to rodent studies, as well as to enhance stress response such as when swimming in cold water. A small experiment reported that ashwagandha could improve memory function in rats. Ashwagandha extract has been reported to promote the formation of dendrites in human neuroblastoma cells.

• Cholinesterase inhibitory potential: In laboratory studies, withanolides 1-3 and 4-5 isolated from Withania somnifera have shown cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay, which could make compounds one to five possible drug candidates for further research to treat Alzheimer’s disease and associated problems.

• Cyclophosphamide toxicity protection effects: Protection of cyclophosphamide toxicity in rodents has been reported, including beneficial effects on bladder mucosa and reduced delayed-type hypersensitivity and myelosuppression.

• Cytotoxic effects: The active withanolide components, withaferins A and D, have anti-inflammatory and antioxidant effects. W. somnifera water and methanol extracts were tested for their cytotoxic effects. The three smallest concentrations (0.007, 0.042 and 0.25 mcg/mL) of the plant extract had a lack of a significantly different effect in the assays. The authors concluded that low concentrations of extracts (up to 0.25 mcg/mL) lacked cytotoxic effects for MRC-5 cells. Higher levels, however, may cause cytotoxic effects.

• Diureticeffects: In a case series, significant increases in urine volume and sodium levels compared to baseline were noted with use of ashwagandha.

• Fertility effects: In humans, W. somnifera decreased oxidative stress. Testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin levels, which are indicators of semen quality, improved in infertile subjects following treatment.

• Hematologic effects: In mice, protective effects against cyclophosphamide and radiation-induced myelosuppression have been noted. Protection against chemotherapy-induced myelosuppression and leukopenia has also been noted in an animal research. Ashwagandha administered for 90 days has been associated with increased hematopoiesis in rats.

• Hormonal effects: Ashwagandha may possess androgenic (testosterone-like) properties, according to rat evidence of increased testicular weight and spermatogenesis.

• Immunologic effects: The ashwagandha constituent withaferin A has been suggested to possess immunosuppressive activity, and in vitro has been found to possess protective effects on peroxide-induced cytotoxicity and DNA damage in human nonimmortalized fibroblasts. Prevention of granuloma formation has been noted in rats. Other authors have reported additional immunomodulatory effects and anti-inflammatory effects in mice and rats, including enhanced cytokine production.

• Neuroprotective effects: In vivo, withanolide A, and withanosides IV and VI (10 mcmol/kg daily for 12 days) restored pre- and postsynapses in cortical neuron axons and dendrites following Abeta(25-35)-induced injury. Impaired memory, neurite atrophy, and synaptic loss improved. In mice with spinal chord injury, withanoside IV benefited locomotor functions. In mice, withanoside IV (10 mcmol/kg daily for 21 days) increased axonal density and peripheral nervous system myelin.

• Protein synthesis effects: Ashwagandha administration was reported to decrease synthesis of alpha-2-macroglobulin and enhancement of total proteins in rats.

• Thyroid effects: Ashwagandha has been reported to stimulate thyroid function in mice, including increased serum T4 concentrations.

For a full list of references, visit www.naturalpractitionermag.com.

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Mikolai, J., Erlandsen, A., Murison, A., Brown, K. A., Gregory, W. L., Raman-Caplan, P., and Zwickey, H. L. In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes. J.Altern.Complement Med. 2009;15(4):423-430. View abstract.

32530

Bhat, J., Damle, A., Vaishnav, P. P., Albers, R., Joshi, M., and Banerjee, G. In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. Phytother.Res 2010;24(1):129-135. View abstract.

32531

Yu, Y., Hamza, A., Zhang, T., Gu, M., Zou, P., Newman, B., Li, Y., Gunatilaka, A. A., Zhan, C. G., and Sun, D. Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem.Pharmacol. 2-15-2010;79(4):542-551. View abstract.

32532

Pretorius, E., Oberholzer, H. M., and Becker, P. J. Comparing the cytotoxic potential of Withania somnifera water and methanol extracts. Afr.J.Tradit.Complement Altern.Med. 2009;6(3):275-280. View abstract.

32533

Ven Murthy, M. R., Ranjekar, P. K., Ramassamy, C., and Deshpande, M. Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. Cent.Nerv.Syst.Agents Med.Chem. 9-1-2010;10(3):238-246. View abstract.

32534

Toniolo, M., Ceschi, A., Meli, M., Lohri, A., and Favre, G. Haemolytic anaemia and abdominal pain–a cause not to be missed. Br.J.Clin.Pharmacol. 2011;72(1):168-169. View abstract.

32535

Malviya, N., Jain, S., Gupta, V. B., and Vyas, S. Recent studies on aphrodisiac herbs for the management of male sexual dysfunction–a review. Acta Pol.Pharm. 2011;68(1):3-8. View abstract.

32536

Misico, R. I., Nicotra, V. E., Oberti, J. C., Barboza, G., Gil, R. R., and Burton, G. Withanolides and related steroids. Prog.Chem.Org.Nat.Prod. 2011;94:127-229. View abstract.

32537

Sehgal, V. N., Verma, P., and Bhattacharya, S. N. Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug. Skinmed. 2012;10(1):48-49. View abstract.

32538

Vaishnavi, K., Saxena, N., Shah, N., Singh, R., Manjunath, K., Uthayakumar, M., Kanaujia, S. P., Kaul, S. C., Sekar, K., and Wadhwa, R. Differential activities of the two closely related withanolides, Withaferin A and Withanone: bioinformatics and experimental evidences. PLoS.One. 2012;7(9):e44419. View abstract.

32539

Vanden Berghe, W., Sabbe, L., Kaileh, M., Haegeman, G., and Heyninck, K. Molecular insight in the multifunctional activities of Withaferin A. Biochem.Pharmacol. 11-15-2012;84(10):1282-1291. View abstract.

32540

Begum, V. H. and Sadique, J. Effect of Withania somnifera on glycosaminoglycan synthesis in carrageenin-induced air pouch granuloma. Biochem Med Metab Biol. 1987;38(3):272-277. View abstract.

32541

Begum, V. H. and Sadique, J. Long term effect of herbal drug Withania somnifera on adjuvant induced arthritis in rats. Indian J Exp Biol. 1988;26(11):877-882. View abstract.

32542

Malhotra, C. L., Mehta, V. L., Das, P. K., and Dhalla, N. S. Studies on Withania-ashwagandha, Kaul. V. The effect of total alkaloids (ashwagandholine) on the central nervous system. Indian J Physiol Pharmacol. 1965;9(3):127-136. View abstract.

32543

Prasad, S. and Malhotra, C. L. Studies on Withania ashwagandha Kaul. VI. The effect of the alkaloidal fractions (acetone, alcohol and water soluble) on the central nervous system. Indian J Physiol Pharmacol. 1968;12(4):175-181. View abstract.

32544

Malhotra, C. L., Mehta, V. L., Prasad, K., and Das, P. K. Studies on Withania ashwagandha, Kaul. IV. The effect of total alkaloids on the smooth muscles. Indian J Physiol Pharmacol. 1965;9(1):9-15. View abstract.

32545

Budhiraja, R. D., Sudhir, S., and Garg, K. N. Cardiovascular effects of a withanolide from Withania coagulans, dunal fruits. Indian J Physiol Pharmacol. 1983;27(2):129-134. View abstract.

32546

Singh, A., Nagpal, B. L., Sukhdev, and Sood, A. Evaluation of cytodiagnosis by imprint method in breast tumours. Indian J Pathol.Microbiol. 1982;25(1):29-33. View abstract.

32547

Anbalagan, K. and Sadique, J. Influence of an Indian medicine (Ashwagandha) on acute-phase reactants in inflammation. Indian J Exp Biol. 1981;19(3):245-249. View abstract.

32548

Devi, P. U., Sharada, A. C., and Solomon, F. E. In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma. Cancer Lett. 8-16-1995;95(1-2):189-193. View abstract.

32549

Grandhi, A., Mujumdar, A. M., and Patwardhan, B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131-135. View abstract.

32550

Praveenkumar, V., Kuttan, R., and Kuttan, G. Chemoprotective action of Rasayanas against cyclosphamide toxicity. Tumori 8-31-1994;80(4):306-308. View abstract.

32551

Devi, P. U., Sharada, A. C., and Solomon, F. E. Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180. Indian J Exp Biol. 1993;31(7):607-611. View abstract.

32552

Sharada, A. C., Solomon, F. E., Devi, P. U., Udupa, N., and Srinivasan, K. K. Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo. Acta Oncol. 1996;35(1):95-100. View abstract.

32553

Ziauddin, M., Phansalkar, N., Patki, P., Diwanay, S., and Patwardhan, B. Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol. 1996;50(2):69-76. View abstract.

32554

Kuttan, G. Use of Withania somnifera Dunal as an adjuvant during radiation therapy. Indian J Exp Biol. 1996;34(9):854-856. View abstract.

32555

Devi, P. U. Withania somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization. Indian J Exp Biol 1996;34(10):927-932. View abstract.

32556

Kulkarni, S. K. and Ninan, I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213-217. View abstract.

32557

Dhuley, J. N. Therapeutic efficacy of Ashwagandha against experimental aspergillosis in mice. Immunopharmacol.Immunotoxicol. 1998;20(1):191-198. View abstract.

32558

Dhuley, J. N. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 1998;60(2):173-178. View abstract.

32559

Kuppurajan K, Rajagopalan SS, Sitoraman R, and et al. Effect of Ashwagandha (Withania somnifera Dunal) on the process of ageing on human volunteers. Journal of Research in Ayurveda and Siddha 1980;1(2):247-258.

32560

Ahumada F, Aspee F, Wikman G, and et al. Withania somnifera extract. Its effect on arterial blood pressure in anaesthetized dogs. Phytotherapy Research 1991;5:111-114.

32561

Upadhaya L and et al. Role of an indigenous drug Geriforte on blood levels of biogenic amines and its significance in the treatment of anxiety neurosis. Acta Nerv Super 1990;32(1):1-5.

32562

Singh N, Nath R, Lata A, and et al. Withania Somnifera (ashwagandha) a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int.J.Crude Drug Res. 1982;20:29-35.

32563

Ghosal S, Lal J, Srivastava R, and et al. Immunomodulatory and CNS effects of sitoindosides 9 and 10, two new glycowithanolides from Withania somnifera. Phytotherapy Research 1989;3(5):201-206.

32564

Venkataraghavan S, Seshadri C, Sundaresan TP, and et al. The comparative effect of milk fortified with Aswagandha, Aswagandha and Punarnava in children – a double-blind study. J Res Ayur Sid 1980;1:370-385.

32565

Asthana A and Raina MK. Pharmacology of Withania somnifera – a review. Indian Drugs 1989;26(5):199-205.

32566

Bhatia P, Rattan S, Cavallius J, and et al. Withania somnifera (ashwagandha), a so-called rejuvenator, inhibits growth and macromolecular synthesis of human cells. Med.Sci.Res. 1987;15:515-516.

32567

Anbalagan K and Sadique J. Withania somnifera (ashwagandha), a rejuvenating herbal drug which controls alpha-2 macroglobulin synthesis during inflammation. Int.J.Crude Drug Res. 1985;23(4):177-183.