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. August 9, 2020;264:113157. doi: 10.1016/j.jep.2020.113157.
Ashwagandha (Withania somnifera, Solanaceae) holds a prominent place among the Ayurvedic Rasayana herbs. As a powerful adaptogen, ashwagandha is highly acclaimed for its ability to enhance the body's resilience to stress, modulate the immune system, and exert anxiolytic effects. This review aims to connect the traditional uses of ashwagandha with what is known about its pharmacological mechanisms and chemical biology.
Ayurveda, India's traditional medicine system, can be traced back to 6000 BC. Ashwagandha’s importance is reflected in the frequency with which it appears in various ancient scriptures of Ayurveda. It has therapeutic uses in Shotha (inflammation), Kashaya (emaciation), Daurbalya (weakness), Vataroga (neurological disorders), and more. Ashwagandha grows in dry parts of India, Sri Lanka, Afghanistan, Baluchistan, and Sind. It also grows in the Mediterranean regions and in the Himalayas at high altitudes. The plant is an evergreen, branching shrub that reaches up to 150 cm. It has ovate, glabrous leaves measuring ~10 cm in length. Up to five green or bright yellow flowers are arranged in axillary, umbellate cymes. Mature, orange-red berries contain yellow seeds. Ashwagandha roots are unbranched and reach 10-17.5 cm in length and 6-12 mm in diameter.
Several withanolides have been isolated from ashwagandha roots and leaves. Withaferine A (WFA) and withanolide D – isolated from ashwagandha roots – possess most of the herb's pharmacological activities. The roots also contain alkaloids, amino acids, volatile oil, and starch. The total alkaloid content has been reported to vary between 0.13-0.31%, and up to 4.3%. A total of 82 metabolites have been identified from the fruit and stem, including phenolic acids, fatty acids, organic acids, aromatic acids, sugars, tocopherols, and withanamides. Ashwagandha leaves have been reported to contain 12 withanolides, five distinct but hitherto unidentified alkaloids, chlorogenic acid, flavonoids, and amino acids.
Ashwagandha possess various pharmacological activities. WFA has demonstrated anti-cancer effects against human melanoma and renal cancer cells in vitro. It also showed potent antiproliferative activity against human pancreatic cancer cell lines and in pancreatic Panc-1 xenografted mice. A 50% ethanolic extract of ashwagandha root, stem and leaves has also demonstrated anti-cancer activity against five human cancer cell lines of four different tissues. Among the extracts, the leaves showed the maximum cytotoxicity effect. Regarding the immunomodulatory activity of ashwagandha, a 75% methanolic root extract was found to increase stem cell proliferation in normal BALB/c mice exposed to a sublethal dose of gamma radiation, demonstrated by reduced leucopenia and increased bone marrow cells. Similarly, a 70% methanolic extract of ashwagandha root extract administered to cyclophosphamide-treated BALB/C mice enhanced levels of immunomodulating cytokines. Several studies in vitro and in vivo have also demonstrated cardioprotective, neuroprotective, anti-aging, antistress, and anti-diabetic activities with ashwagandha root and leaf extracts. Ashwagandha root extract has been administered in rats up to 2000 mg/kg daily with no toxic effects observed for up to 14 days. Oral administration of aqueous, hydroalcoholic, and ethanolic extracts were reported safe in rodents in different doses for 90 days.
Several clinical trials have demonstrated that ashwagandha root supplementation may improve male fertility, increase muscle size and strength, and reduce stress, leading to improvements in insomnia, anxiety, and memory and cognition. The extract has also shown promise for reducing symptoms of depression and anxiety in patients with schizophrenia. The adverse effects of ashwagandha root extract reported in clinical trials include fever, headache, gastrointestinal conditions, and hallucinogenic effects. The safety of long-term ashwagandha supplementation in humans was not discussed.
The United States market for ashwagandha dietary supplements has steadily increased from $4.53 million in 2014 to $12.24 million in 2017. The herb is also popular in the Asia-Pacific region, Japan, Western Europe, and the Middle East. Manufacturing companies for ashwagandha that hold large market shares, include Ixoreal Biomed (Hyderabad, India), AuNutra Industries Inc. (Chino, California), Himalaya Global Holdings Ltd. (Bengaluru, Karnataka, India), Amax NutraSource, Inc. (Eugene, Oregon), Carrubba Inc. (Milford, Connecticut), and Sabinsa Corporation (East Windsor, New Jersey).
Stemming from its ancient use in Ayurveda, ashwagandha has several modern applications for targeted heath solutions. As the market for ashwagandha continues to climb, the scientific community should prioritize studies that address the efficacy and safety of ashwagandha for its many purported health benefits. Additionally, there should be increased awareness around the responsible use of ashwagandha and ways to reduce quality control issues across the supply chain.
The authors report no conflicts of interest.
–Gavin Van De Walle, MS, RDN