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Cited by 63Phytochemicals and Medicinal PlantsPlant Toxicity and Pharmacological PropertiesDrug-Induced Hepatotoxicity and Protection

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DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha)

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Siddiqui, Shazia, Ahmed, Nabeel, Goswami, Mausumi, Chakrabarty, Anindita, Chowdhury, Goutam·2021·Current Research in Toxicology
DOI 10.1016/j.crtox.2021.02.002PMC PMC8320610
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Abstract

Withania somnifera, commonly known as Ashwagandha, is a medicinal plant used for thousands of years for various remedies. Extracts of Ashwagandha contain more than 200 metabolites, with withanone (win) being one of the major ones responsible for many of its medicinal properties. Recently, several cases of liver toxicity resulting from commercially available Ashwagandha products have been reported. The first report of Ashwagandha-related liver damage was from Japan, which was quickly resolved after drug-withdrawal. Later, similar cases of liver toxicity due to Ashwagandha consumption were reported from the USA and Iceland. Towards understanding the liver toxicity of Ashwagandha extracts, we studied win, a representative withanolide having toxicophores or structural alerts that are commonly associated with adverse drug reactions. We found that win can form non-labile adducts with the nucleosides dG, dA, and dC. Using various biochemical assays, we showed that win forms adducts in DNA and interfere with its biological property. Win also forms adducts with amines and this process is reversible. Based on the data presented here we concluded that win is detoxified by GSH but under limiting GSH levels it can cause DNA damage. The work presented here provides a potential mechanism for the reported Ashwagandha-mediated liver damage.

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  • The underlying mechanism for liver damage due to ashwagandha could be the presence of herb-specific compounds called withanolides that cause irreversible adduction to hepatocellular DNA.

    “The underlying mechanism for liver damage due to ashwagandha could be the presence of herb-specific compounds called withanolides that cause irreversible adduction to hepatocellular DNA.30”

    From Ashwagandha-induced liver injury—A case series from India and literature review (2023) · cites this paper as [30]

    The Conclusions report that withanone, one ashwagandha withanolide, forms non-labile DNA adducts and propose this as a possible explanation for reported liver damage. The Experimental section describes adduct tests using isolated calf thymus DNA, not hepatocellular DNA. The paper therefore supports a potential mechanism, but not the claim that withanolides as a class cause irreversible adduction in liver cells. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Metadata

Authors
Siddiqui, S., Ahmed, N., Goswami, M., Chakrabarty, A., & Chowdhury, G.
Affiliations
  • Shiv Nadar University (IN)
  • Vellore Institute of Technology University (IN)
Corresponding author
Chowdhury, Goutam
ORCID
Venue
Current Research in Toxicology
Publisher
Elsevier BV
Published
2021
Volume
2
Pages
72-81
ISSN
2666-027X (ISSN-L)
DOI
10.1016/j.crtox.2021.02.002
PMC
PMC8320610
OpenAlex
W3132676081
Cited by
63
References
3
Citations by year
2026: 17 · 2025: 11 · 2024: 14 · 2023: 10 · 2022: 7 · 2021: 2
FWCI
9.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Research in Toxicology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Department of Science and Technology, Ministry of Science and Technology, India (ECR/2015/000197, ECR/2015/000198)
  • Science and Engineering Research Board
  • Department of Biotechnology, Ministry of Science and Technology, India (BT/RLF/RE-ENTRY/18/2013, BT/RLF/RE-ENTRY/35/2012)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Plant Toxicity and Pharmacological Properties
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
withanone, Withania somnifera, hepatotoxicity, DNA adducts, DNA damage, withanolides, nucleoside adducts, glutathione detoxification, adverse drug reactions, toxicophores

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