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Review
. 2023 Mar 29:14:1049334.
doi: 10.3389/fphar.2023.1049334. eCollection 2023.

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

Arsalan Bashir  1 , Masarat Nabi  2 , Nahida Tabassum  1 , Suhaib Afzal  1 , Mehrose Ayoub  1
Affiliations
Review

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

Arsalan Bashir et al. Front Pharmacol. .

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.

Keywords: Withania somnifera (L.) Dunal; apoptosis; molecular targets; phytochemistry; withaferin A; withanolides.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Different compound classes of W. somnifera.
FIGURE 2
FIGURE 2
Anti-inflammatory mechanism of bioactive constituents of W. somnifera.
FIGURE 3
FIGURE 3
Anticancer mechanism of bioactive constituents of W. somnifera.
FIGURE 4
FIGURE 4
Neuroprotective mechanism of bioactive constituents of W. somnifera.
See this image and copyright information in PMC

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