DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha)
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 ca...
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ftpubmed:oai:pubmedcentral.nih.gov:8320610 2023-05-15T16:50:39+02:00 DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) Siddiqui, Shazia Ahmed, Nabeel Goswami, Mausumi Chakrabarty, Anindita Chowdhury, Goutam 2021-02-16 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320610/ http://www.ncbi.nlm.nih.gov/pubmed/34345852 https://doi.org/10.1016/j.crtox.2021.02.002 en eng Elsevier http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320610/ http://www.ncbi.nlm.nih.gov/pubmed/34345852 http://dx.doi.org/10.1016/j.crtox.2021.02.002 © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). CC-BY-NC-ND Curr Res Toxicol Article Text 2021 ftpubmed https://doi.org/10.1016/j.crtox.2021.02.002 2021-08-08T00:43:40Z 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. Text Iceland PubMed Central (PMC) Current Research in Toxicology 2 72 81 |
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Article Siddiqui, Shazia Ahmed, Nabeel Goswami, Mausumi Chakrabarty, Anindita Chowdhury, Goutam DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
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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. |
format |
Text |
author |
Siddiqui, Shazia Ahmed, Nabeel Goswami, Mausumi Chakrabarty, Anindita Chowdhury, Goutam |
author_facet |
Siddiqui, Shazia Ahmed, Nabeel Goswami, Mausumi Chakrabarty, Anindita Chowdhury, Goutam |
author_sort |
Siddiqui, Shazia |
title |
DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
title_short |
DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
title_full |
DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
title_fullStr |
DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
title_full_unstemmed |
DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
title_sort |
dna damage by withanone as a potential cause of liver toxicity observed for herbal products of withania somnifera (ashwagandha) |
publisher |
Elsevier |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320610/ http://www.ncbi.nlm.nih.gov/pubmed/34345852 https://doi.org/10.1016/j.crtox.2021.02.002 |
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Iceland |
genre_facet |
Iceland |
op_source |
Curr Res Toxicol |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320610/ http://www.ncbi.nlm.nih.gov/pubmed/34345852 http://dx.doi.org/10.1016/j.crtox.2021.02.002 |
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© 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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CC-BY-NC-ND |
op_doi |
https://doi.org/10.1016/j.crtox.2021.02.002 |
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Current Research in Toxicology |
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