An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha)

Abstract

Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000 years. It is a rich reservoir of pharmaceutically bioactive constituents known as withanolides (a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton). Most of the biological activities of W. somnifera have been attributed to two key withanolides, namely, withaferin-A and withanolide-D. In addition, bioactive constituents such as withanosides, sitoindosides, steroidal lactones, and alkaloids are also present with a broad spectrum of therapeutic potential. Several research groups worldwide have discovered various molecular targets of W. somnifera, such as inhibiting the activation of nuclear factor kappa-B and promoting apoptosis of cancer cells. It also enhances dopaminergic D2 receptor activity (relief in Parkinson’s disease). The active principles such as sitoindosides VII-X and withaferin-A possess free radical properties. Withanolide-D increases the radio sensitivity of human cancer cells via inhibiting deoxyribonucleic acid (DNA) damage to non-homologous end-joining repair (NHEJ) pathways. Withanolide-V may serve as a potential inhibitor against the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to combat COVID. The molecular docking studies revealed that the withanolide-A inhibits acetyl-cholinesterase in the brain, which could be a potential drug to treat Alzheimer’s disease. Besides, withanolide-A reduces the expression of the N-methyl-D-aspartate (NMDA) receptor, which is responsible for memory loss in epileptic rats. This review demonstrates that W. somnifera is a rich source of withanolides and other bioactive constituents, which can be used as a safe drug for various chronic diseases due to the minimal side effects in various pre-clinical studies. These results are interesting and signify that more clinical trials should be conducted to prove the efficacy and other potential therapeutic effects in human settings.

Elicitation boosts withaferin A and withanolide A production in Withania somnifera (L.) Dunal hairy root cultures

“…These roots are prized for their rejuvenating effects, serving as a strengthening tonic, promoting weight gain, acting as aphrodisiacs, and alleviating bleeding disorders. Key bioactive constituents within W. somnifera roots include withanosides, sitoindosides, withanolides, and alkaloids, as supported by various studies (Paul et Bashir et al 2023). Notably, the roots harbor a wealth of bene cial chemical compounds unique to W. somnifera, making them particularly valued for medicinal purposes (Shinde et al 2023).…”

Neuropsychopharmacological Induction of (Lucid) Dreams: A Narrative Review

“…They also cite anti-Alzheimer properties-inhibition of AChE and enhanced choline acetyltransferase level in rats-which are an effect of the active compound whitaferin-A (withanolide). Increased cholinergic transmission in the basal ganglia and cerebral cortex might explain the cognition improvements induced by these substances [81]. The ethanolic root extract improved gripping ability and motor movements, as well as increasing striatum DA in rats.…”

“…Major bioactive compounds are steroidal lactones, called withanolides, which are potent antioxidants together with alkaloids. Restoring spatial memory, motor learning, muscarinic receptor activation, and oxidative stress are cited in Bashir and colleague's recent review [81]. They also cite anti-Alzheimer properties-inhibition of AChE and enhanced choline acetyltransferase level in rats-which are an effect of the active compound whitaferin-A (withanolide).…”

“…The ethanolic root extract improved gripping ability and motor movements, as well as increasing striatum DA in rats. Another ethanolic root extract had neuroprotective effects on nigrostriatal dopaminergic neurons [81].…”