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Life Force Constituents:

This is the summary of uses from Memorial Sloan Kettering Cancer Center

Ashwagandha


Scientific Name
Withania somnifera
Common Name

Ashwagandha, Indian ginseng, Winter cherry

Clinical Summary

A popular Ayurvedic herb, ashwagandha is often used in formulations prescribed for stress, strain, fatigue, pain, skin diseases, diabetes, gastrointestinal disease, rheumatoid arthritis, and epilepsy (1). It is also used as a general tonic, to increase energy and improve health and longevity (2). Externally, it can be applied as a local analgesic (3). The active constituents are thought to include alkaloids, steroidal lactones, saponins, and withanolides.

In vitro studies suggest that ashwagandha has neuroprotective (26) and anti-inflammatory properties which may protect against cartilage damage in osteoarthritis (4). Animal studies suggest antitumor, immunomodulatory, antioxidant, and anti-stress properties. In addition, improvements in hyperglycemia, hyperinsulinemia, and insulin sensitivity have been detected in an animal model of type 2 diabetes (5). Other studies indicate cytotoxic, chemopreventative, immunomodulating (8), and radiosensitizing effects (1)(9)(10) and enhancement in chromosomal stability (11).

Ashwagandha is rich in iron (2); small scale human studies suggest that it may promote growth in children and improve hemoglobin level, red blood cell count, sexual performance in adults (2), and may also be useful in treating male infertility (27). An herbal tea containing ashwagandha was shown to increase natural killer cell activity in healthy volunteers with recurrent coughs and colds (22). Data also indicate that ashwagandha may be useful in the treatment of anxiety (23). In another clinical trial, an herbomineral formula containing ashwagandha was shown to benefit osteoarthritis (13). Preliminary data suggest benefits of ashwagandha in improving balance in patients with progressive degenerative cereberral ataxias (24).

Ashwagandha also reduced growth of breast, central nervous system, colon, and lung cancer cells (6) without affecting normal cells (7). Ashwagandha may help prevent chemotherapy-induced neutropenia (12), but it has not been studied in cancer patients.

Purported Uses
  • Cancer treatment
  • Diabetes
  • Epilepsy
  • Fatigue
  • GI disorders
  • Health maintenance
  • Pain
  • Rheumatoid arthritis
  • Sedation
  • Skin infections
  • Stress
Constituents
  • Alkanoids: isopelletierine, anaferine
  • Steroidal lactones: withanolides (withaferin-A, 12-deoxywithastramonolide, and withanolide-A), withaferins
  • Saponins: sitoindoside VII and VIII, Iron
    (2)
Mechanism of Action

Alkaloids, steroidal lactones, saponins, and withanolides are thought to be the biologically active components of ashwagandha. Studies have pointed to cyclooxygenase (COX) inhibition as the mechanism for the herb's antiarthritic properties. In animal studies, Ashwagandha's anti-inflammatory effects were comparable to hydrocortisone (15). Microarray analysis revealed that ashwagandha represses proinflammatory gene expression, including IL-6, IL-1β, IL-8, Hsp70, and STAT-2, and induces p38/MAPK expression in a prostate cancer cell line (16). It exhibits antioxidant effects in the brain and tranquilizing effects on the central nervous system in animals (2) possibly by influencing GABA receptor function (17). Ashwagandha may inhibit tumor growth (1)(21)and increases cytotoxic T lymphocyte production (8). In vitro studies have shown that root extracts have cytotoxic properties against lung, colon, central nervous system, and breast cancer cell lines (6). Withaferin A induces reactive oxygen species (ROS) generation and disruption of mitochondrial function in a human leukemia cell line, thereby inducing apoptosis (18). In estrogen receptor-positive (ER+) and negative (ER-) breast cancer cells, withaferin A induces apoptosis and decreased tumor size (19). Apoptosis of cancer cells by withanone is mediated through p53 (7). Other studies show ashwagandha's cytotoxicity is related to its structure; it enhances ATPase and inhibits succinate dehydrogenase activities, impairing oxidative phosphorylation. In animal studies, ashwagandha can enhance the effects of radiation therapy (20) by reducing tumor GSH levels (10). Ashwagandha can reverse paclitaxel-induced neutropenia in mice (12). Significant toxicity was observed at high doses in animal studies (20); however, toxicity studies in humans are limited (2).

Contraindications

Pregnant women should avoid ashwagandha as it may induce abortion (14).

Adverse Reactions

Case Report: Thyrotoxicosis was reported in a 32-year-old woman following ingestion of ashwagandha capsules for chronic fatigue. Her symptoms resolved after discontinuing ashwagandha (25).

Herb-Drug Interactions

May potentiate the sedative effect of barbiturates (14).

Literature Summary and Critique

This study was conducted to determine the effect of naturopathic care on releiving anxiety. Eighty-one participants with moderate to severe anxiety lasting longer than 6 weeks were randomized to receive naturopathic care (NC) or standardized psychotherapy intervention (PT) for 12 weeks. The NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% with anolides, prepared from root); those in the PT group received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Researchers reported a significant reduction in the BAI scores in NC group compared to those in PT group (p = 0.003). Significant differences were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life between groups with the NC group faring better.
However, it is not clear if Ashwagandha alone would yield similiar benefit. Some limitations of this study include small sample size, absence of a control group, and data based on patient reported symptoms. Larger, well designed studies are warranted.

References
  1. Prakash J, Gupta SK, Dinda AK. Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of skin in Swiss albino mice. Nutr Cancer. 2002;42(1):91-97.
  2. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. Aug 2000;5(4):334-346.
  3. Dafni A, Yaniv Z. Solanaceae as medicinal plants in Israel. J Ethnopharmacol. Aug 1994;44(1):11-18.
  4. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. Oct 2008;22(10):1342-1348.
  5. Anwer T, Sharma M, Pillai KK, et al. Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats. Basic Clin Pharmacol Toxicol. Jun 2008;102(6):498-503.
  6. Jayaprakasam B, Zhang Y, Seeram NP, et al. Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves. Life Sci. Nov 21 2003;74(1):125-132.
  7. Widodo N, Kaur K, Shrestha BG, et al. Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect. Clin Cancer Res. Apr 1 2007;13(7):2298-2306.
  8. Davis L, Kuttan G. Effect of Withania somnifera on CTL activity. J Exp Clin Cancer Res. Mar 2002;21(1):115-118.
  9. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. Feb 11 1983;249(6):751-757.
  10. Devi PU. Withania somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization. Indian J Exp Biol. Oct 1996;34(10):927-932.
  11. Panjamurthy K, Manoharan S, Menon VP, et al. Protective role of withaferin-A on 7,12-dimethylbenz(a)anthracene-induced genotoxicity in bone marrow of Syrian golden hamsters. J Biochem Mol Toxicol. Jul 2008;22(4):251-258.
  12. Gupta YK, Sharma SS, Rai K, et al. Reversal of paclitaxel induced neutropenia by Withania somnifera in mice. Indian J Physiol Pharmacol. Apr 2001;45(2):253-257.
  13. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. May-Jun 1991;33(1-2):91-95.
  14. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy (OR): Eclectic Medical Publications; 2001.
  15. al-Hindawi MK, al-Khafaji SH, Abdul-Nabi MH. Anti-granuloma activity of Iraqi Withania somnifera. J Ethnopharmacol. Sep 1992;37(2):113-116.
  16. Aalinkeel R, Hu Z, Nair BB, et al. Genomic Analysis Highlights the Role of the JAK-STAT Signaling in the Anti-proliferative Effects of Dietary Flavonoid -'Ashwagandha' in Prostate Cancer Cells. Evid Based Complement Alternat Med. 2010 Jun;7(2):177-87.
  17. Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system. Indian J Exp Biol. Jun 2008;46(6):465-469.
  18. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. Nov 2007;12(11):2115-2133.
  19. Stan SD, Hahm ER, Warin R, et al. Withaferin A causes FOXO3a- and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. Sep 15 2008;68(18):7661-7669.
  20. Devi PU, Sharada AC, Solomon FE. In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma. Cancer Lett. Aug 16 1995;95(1-2):189-193.
  21. Devi PU, Sharada AC, Solomon FE. Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180. Indian J Exp Biol. Jul 1993;31(7):607-611.
  22. Bhat J, Damle A, Vaishnav PP, et al. In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. Phytother Res. 2010 Jan;24(1):129-35.
  23. Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009 Aug 31;4(8):e6628.
  24. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: a preliminary report. Neurol India. 2009 Mar-Apr;57(2):166-71.
  25. van der Hooft CS, Hoekstra A, Winter A, et al. [Thyrotoxicosis following the use of ashwagandha]. Ned Tijdschr Geneeskd. 2005 Nov 19;149(47):2637-8.
  26. Kumar S, Harris RJ, Seal CJ, Okello EJ. An Aqueous Extract of Withania somnifera Root Inhibits Amyloid � Fibril Formation In Vitro. Phytother Res. 2011 May 12. doi: 10.1002/ptr.3512. [Epub ahead of print]
  27. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010 Aug;94(3):989-96.