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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ftdoajarticles:oai:doaj.org/article:850069fd257e4ae9b5fa26d316334808 2023-05-15T16:50:56+02:00 DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) Shazia Siddiqui Nabeel Ahmed Mausumi Goswami Anindita Chakrabarty Goutam Chowdhury 2021-01-01T00:00:00Z https://doi.org/10.1016/j.crtox.2021.02.002 https://doaj.org/article/850069fd257e4ae9b5fa26d316334808 EN eng Elsevier http://www.sciencedirect.com/science/article/pii/S2666027X21000074 https://doaj.org/toc/2666-027X 2666-027X doi:10.1016/j.crtox.2021.02.002 https://doaj.org/article/850069fd257e4ae9b5fa26d316334808 Current Research in Toxicology, Vol 2, Iss , Pp 72-81 (2021) Ashwagandha DNA damage Withanone Toxicity Glutathione Toxicology. Poisons RA1190-1270 article 2021 ftdoajarticles https://doi.org/10.1016/j.crtox.2021.02.002 2022-12-31T12:39:22Z 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. Article in Journal/Newspaper Iceland Directory of Open Access Journals: DOAJ Articles Current Research in Toxicology 2 72 81 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Ashwagandha DNA damage Withanone Toxicity Glutathione Toxicology. Poisons RA1190-1270 |
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Ashwagandha DNA damage Withanone Toxicity Glutathione Toxicology. Poisons RA1190-1270 Shazia Siddiqui Nabeel Ahmed Mausumi Goswami Anindita Chakrabarty Goutam Chowdhury DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha) |
topic_facet |
Ashwagandha DNA damage Withanone Toxicity Glutathione Toxicology. Poisons RA1190-1270 |
description |
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 |
Article in Journal/Newspaper |
author |
Shazia Siddiqui Nabeel Ahmed Mausumi Goswami Anindita Chakrabarty Goutam Chowdhury |
author_facet |
Shazia Siddiqui Nabeel Ahmed Mausumi Goswami Anindita Chakrabarty Goutam Chowdhury |
author_sort |
Shazia Siddiqui |
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 |
https://doi.org/10.1016/j.crtox.2021.02.002 https://doaj.org/article/850069fd257e4ae9b5fa26d316334808 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Current Research in Toxicology, Vol 2, Iss , Pp 72-81 (2021) |
op_relation |
http://www.sciencedirect.com/science/article/pii/S2666027X21000074 https://doaj.org/toc/2666-027X 2666-027X doi:10.1016/j.crtox.2021.02.002 https://doaj.org/article/850069fd257e4ae9b5fa26d316334808 |
op_doi |
https://doi.org/10.1016/j.crtox.2021.02.002 |
container_title |
Current Research in Toxicology |
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2 |
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72 |
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81 |
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1766041049125355520 |