Ashwagandha (Withania somnifera)

The name ‘Ashwagandha’ is derived from the Sanskrit word ‘Ashva,’ meaning horse, and ‘gandh’ denoting smell referring to the horse-like odor emanating from its root. Its scientific name is Withania somnifera, a plant in the Solanaceae (Tomato family). Withania is named after Henry Witham, an English palaeobotanist of the early 19th century. The species name somnifera denotes “sleep-inducing” in Latin.

Ashwagandha (Withania somnifera)

Uses

Ashwagandha is often used in formulations prescribed for sleep, stress, strain, fatigue, pain, skin diseases, diabetes, gastrointestinal disease, rheumatoid arthritis, and epilepsy. It is also employed as a general tonic to improve energy levels, health, and longevity, and topically as an analgesic. Active constituents include alkaloids, steroidal lactones, saponins, and unique withanolides.

Chemistry/Pharmacology

The herb is composed of alkaloids, steroidal lactones, and saponins, many of which support immunomodulatory actions.nia.

Clinical Studies

There have been extensive studies performed on ashwaganda, particularly in India owing to its long historic usage in Ayurvedic medicine. In vitro studies suggest that ashwagandha has neuroprotective and anti-inflammatory properties which may protect against cartilage damage in osteoarthritis. In addition, improvements in hyperglycemia, hyperinsulinemia, and insulin sensitivity were observed in a murine model of type 2 diabetes. Other studies indicate cytotoxic, immunomodulating, chemopreventive, and radiosensitizing effects, and enhancement in chromosomal stability.

Small clinical studies suggest that ashwagandha may promote growth, hemoglobin level, and red blood cell count in children, as well as sexual performance and male infertility in adults. Findings also indicate that it may help relieve anxiety; stress; and improve both non-restorative sleep and sleep quality in patients with insomnia. In patients with schizophrenia, adjunctive treatment with ashwagandha improved symptoms and stress and affected markers of metabolic syndrome. Ashwagandha was also reported to have beneficial effects on cognitive function in patients with bipolar disorder. Preliminary data suggest that it may help to improve balance in patients with progressive degenerative cerebral ataxias.

Ashwagandha has also demonstrated anticancer effects against several cancer cell lines. It prevented chemotherapy-induced neutropenia in a murine model; and the compound Withaferin A enhanced oxaliplatin effects in human pancreatic cancer cells. In a small study of breast cancer patients, ashwagandha alleviated chemotherapy-induced fatigue and improved quality of life.

Alkaloids, steroidal lactones, saponins, and withanolides are considered the biologically active components of ashwagandha. Anti-arthritic effects are attributed to cyclooxygenase (COX) inhibition.

In animal studies, anti-inflammatory activity by ashwagandha was comparable to hydrocortisone. Brain antioxidant effects and CNS tranquilizing effects may be due to influences on GABA receptor function. Withanolides in the roots and leaves are considered similar to steroids in their biological activities. Triethylene glycol, a compound isolated from the leaves, was identified as an active sleep-inducing component in a murine model and may potentially be used to relieve insomnia.

Biomechanical Mechanism

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 prostate cancer cell line. Ashwagandha may inhibit tumor growth and increased cytotoxic T lymphocyte production. In vitro studies show that root extracts have cytotoxic properties against lung, colon, CNS, and breast cancer cell lines. Withaferin-A induced reactive oxygen species (ROS) generation and disruption of mitochondrial function in a human leukemia cell line, thereby inducing apoptosis. In estrogen receptor-positive (ER+) and negative (ER-) breast cancer cells, withaferin-A induced apoptosis and decreased tumor size. Apoptosis of cancer cells by withanone is mediated through p53. Withianone also exerts anticancer activity by binding to the TPX2-Aurora-A Complex. Other studies show ashwagandha cytotoxicity is related to its structure. It enhances ATPase and inhibits succinate dehydrogenase activities, impairing oxidative phosphorylation.

In animal studies, ashwagandha enhanced radiation therapy effects by reducing tumor GSH levels and reversed paclitaxel-induced neutropenia in mice. No significant interactions have been reported between ashwagandha and either CYP3A4 or CYP2D6 enzymes in human liver microsomes.

Sources/Articles

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.

Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma oinfertile males. Fertil Steril. 2010;94(3):989-96.

al-Hindawi MK, al-Khafaji SH, Abdul-Nabi MH. Anti-granuloma activity of Iraqi Withania somnifera. J Ethnopharmacol. 1992;37(2):113-116.

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. 2008;102(6):498-503.

Biswal BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI. Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients. Integr Cancer Ther. 2013;12(4):312-22.

Chengappa KNR, Brar JS, Gannon JM, et al. Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. Jul 10 2018;79(5).

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Gannon JM, Forrest PE, Roy Chengappa KN. Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder. J Ayurveda Integr Med. 2014;5:241-245.

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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.

Jayaprakasam B, Zhang Y, Seeram NP, et al. Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves. Life Sci. 2003;74(1):125-132.

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. 1991;33(1-2):91-95.

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. 2008;46(6):465-469.

Kumar S, Harris RJ, Seal CJ, Okello EJ. An aqueous extract of Withania somnifera root inhibits amyloid β fibril formation in vitro. Phytother Res. 2012;26(1):113-7.

Langade D, Thakare V, Kanchi S, Kelgane S. Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel-group, placebo-controlled study. J Ethnopharmacol. 2021 Jan 10;264:113276.

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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.

Ramakanth GS, Uday Kumar C, Kishan PV, et al. A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain. J Ayurveda Integr Med. Jul - Sep 2016;7(3):151-157.

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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. 2008;68(18):7661-7669.

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. 2008;22(10):1342-1348.

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