DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha)
| Autor: | Goutam Chowdhury, Anindita Chakrabarty, Nabeel Ahmed, Shazia Siddiqui, Mausumi Goswami |
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| Rok vydání: | 2021 |
| Předmět: |
Liver toxicity
DNA damage Health Toxicology and Mutagenesis Ashwagandha Biology Withania somnifera Toxicology Applied Microbiology and Biotechnology Article EDTA ethylenediamine tetraacetic acid chemistry.chemical_compound RA1190-1270 HDS Herbal medicines and dietary supplements Biological property GSH glutathione Liver damage ComputingMethodologies_COMPUTERGRAPHICS Toxicity Traditional medicine Glutathione Withanone biology.organism_classification Win withanone LC–MS liquid chromatography-mass spectrometry Withanolide chemistry Toxicology. Poisons DMEDA dimethylethylenediamine cys cysteine |
| Zdroj: | Current Research in Toxicology Current Research in Toxicology, Vol 2, Iss, Pp 72-81 (2021) |
| ISSN: | 2666-027X |
| DOI: | 10.1016/j.crtox.2021.02.002 |
| Popis: | Graphical abstract Highlights • The widely used medicinal herb Withania somnifera (Ashwagandha) has been recently reported to cause liver damage. • Withanone is a major metabolite of Ashwagandha. • Withanone was found to cause DNA damage. • Withanone forms adducts with amines and thiols. • Withanone-mediated DNA damage has serious biological consequences. 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. |
| Databáze: | OpenAIRE |
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