Mukherjee PK, Banerjee S, Biswas S, Das B, Kar A, Katiyar CK. Withania somnifera (L.) Dunal – modern perspectives of an ancient rasayana from Ayurveda. J Ethnopharmacol. January 10, 2021;264:113157. doi: 10.1016/j.jep.2020.113157.
Ashwagandha (Withania somnifera, Solanaceae) root is the most prominent “Rasayana” in the traditional medical system of India (IN), Ayurveda, and is known primarily for being an adaptogenic tonic. Ayurveda developed from the Vedas, an ancient body of Hindu religious texts traced back to 6000 BCE. According to these ancient manuscripts, ashwagandha is clinically useful in inflammation, emaciation, skin problems, constipation, insomnia, rheumatism, goiter, tuberculosis, glandular diseases, pain, epilepsy, snakebite or scorpion sting, intestinal parasites, hemorrhoids, gynecological problems, weakness, neurological disorders, cough, asthma, wounds, hysteria, memory loss, fainting, and as a general health tonic. Ashwagandha is included in more than 60 traditional herbal formulas. It is reported to benefit the brain and nervous system, sexual performance and reproductive function, and cell-mediated immunity. It has anxiolytic, antioxidant, anti-aging, diuretic, aphrodisiac, spermatogenic, and hepatoprotective properties. It raises hemoglobin and red blood cell counts and boosts energy. The authors attempt to summarize ancient knowledge and modern research findings about ashwagandha. Unfortunately, many Ayurvedic terms in the article are not translated.
Ashwagandha, an evergreen shrub, grows wild and cultivated in arid regions of IN, Sri Lanka, Afghanistan, Pakistan, the Canary Islands, Mediterranean basin, Cape of Good Hope, and the Himalayas at ≤ 5000 feet above sea level. Mature roots are collected in winter, washed, dried, and cut into small pieces for storage. Their strong, bitter aroma, likened to horse urine, is the source of the plant's Sanskrit name, “Ashwa.” Freshly ground root powder mixed with water is used topically; powder is taken orally with food or milk.
Three ashwagandha chemotypes identified in Israel have differing steroidal lactones of withanolides. Indian and Italian studies found chemotypes similar but not identical to those identified in Israel; other chemotypes may be possible. Root, shoot, and leaf extracts have yielded 12 alkaloids, 35 withanolides, and several sitoindosides. Much of ashwagandha’s pharmacological activity is credited to withaferin A(1), the first natural lactone of the withanolide series identified, with withanolide D(2). Withaferin A(1) and sitoindosides IX(3) – X(4) have significant anti-stress effects. Various plant parts contain withaniol, acylsterylglucosides, starches, sugars, hentriacontane, ducitol, amino acids, volatile oils, saponins, and iron. Chemical structures of 31 ashwagandha molecules are shown. Withanolides are structurally similar to the ginsenosides characteristic of Asian ginseng (Panax ginseng, Araliaceae) and related species. Roots, fruits, stems, and leaves have been analyzed for chemical content, all containing withanolides in addition to a plethora of other compounds. A study of ashwagandha fruits found 82 metabolites. Leaves contain chlorogenic acid, condensed tannins, and flavonoids.
These compounds give ashwagandha its range of pharmacological activity. In vitro and in vivo studies report its anti-cancer, anti-diabetic, immunomodulatory, cardioprotective, neuroprotective, antioxidant/anti-aging, and anti-stress/adaptogenic effects. Clinical trials, all using root extracts, report benefits in memory and cognition, subclinical hypothyroidism, schizophrenia, chronic stress/anxiety/insomnia, obsessive-compulsive disorder, type 2 diabetes, male infertility, and physical strength and performance. Eleven modern ashwagandha formulations available on the market are listed.
Oral intake of aqueous, hydroalcoholic, and ethanolic ashwagandha root extracts are non-toxic in acute and sub-acute in vivo studies, with no changes in mortality, stress, food intake, body weight, normal or aversive behavior, or non-sexual behavior in male rats. There were no changes in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or bilirubin, nor pathological lesions in any organ. Intraperitoneal (i.p.) administration of ethanolic extract (100 mg/kg body weight [[bw]/d for 30 days) increased hemoglobin, red blood counts, and acid phosphatase activity in rats of both gender and significantly decreased weight of spleen, adrenals, and thymus in males only. Withaferin A (50 mg/kg bw/d, i.p.), sitoindoside IX, and sitoindoside (50 mg/kg bw/d, i.p.) first initiated central nervous system depression, followed by stimulation. The lethal dose (LD)50 of several constituents, given intraperitoneally and orally, has been established in rodents.
The market for ashwagandha products is enormous and growing. In the United States (US), sales rose from $4.53 million in 2014 to an estimated $12.24 million in 2017, an annual increase of ~ 39%. In October 2018, the price of high-quality dried roots in IN ranged from US $2.46 – 3.46/oz, with low grade roots and dried leaves as little as $1.50 and $0.34/0z, respectively. Major global corporations share the manufacturing market. Popular supplements in the Asian Pacific, North America, Japan, Western Europe, and the Middle East contain ashwagandha. Germany is investing significantly in botanical medicine research, including Ayurvedic herbs such as ashwagandha. Among novel products, an ashwagandha-containing, pasteurized, and homogenized product, Amul Memory Milk (Gujarat Cooperative Milk Marketing Federation; Anand, Gujarat, IN), is sold as a memory enhancer. Other ashwagandha functional foods may be developed. While ashwagandha has been a valued medicine for > 6000 years of human history, and pharmacological studies have verified many of its traditional uses, additional clinical trials are needed to substantiate some of its reported effects. Data on ashwagandha's mechanisms of action, pharmacokinetics, potential adverse effects, and drug interactions are limited. Quality control measures are needed. Public awareness of its verified uses should be stimulated to protect its identity and quality.