ArticleBiochemical pharmacology2015
Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 78 citations in OpenAlex.
- From a Multi-Omics Signature to a Therapeutic Candidate: Computational Prediction and Experimental Validation in Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Effects of ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: A randomized, double-blinded placebo-controlled study.Veterinary medicine and science · 2024Article
- Withaferin-A attenuates diabetes mellitus induced male reproductive dysfunction mediated by ERα in brain and testes of Swiss albino mice.Scientific reports · 2023Article
- Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice.World journal of gastroenterology · 2023Article
- Targeting Metabolic Syndrome in Hidradenitis Suppurativa by Phytochemicals as a Potential Complementary Therapeutic Strategy.Nutrients · 2023Review
- Chantriolides F-P, Highly Oxidized Withanolides with Hepatoprotective Activity fromMolecules (Basel, Switzerland) · 2022Article
- Antioxidant and hepatoprotective effects of novel heteropolysaccharide isolated fromFood science & nutrition · 2022Article
- Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma.Scientific reports · 2022Article
- Withaferin A alleviates ethanol-induced liver injury by inhibiting hepatic lipogenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Article
- A bioactive ligand-conjugated iridium(III) metal-based complex as a Keap1-Nrf2 protein-protein interaction inhibitor against acetaminophen-induced acute liver injury.Redox biology · 2021Article
- Rosmarinic acid ameliorates acetaminophen-induced acute liver injury in mice via RACK1/TNF-α mediated antioxidant effect.Pharmaceutical biology · 2021Article
- Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury.World journal of gastroenterology · 2021Review
- Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3.Cell death & disease · 2021Article
- Tackling Chronic Inflammation with Withanolide Phytochemicals-A Withaferin a Perspective.Antioxidants (Basel, Switzerland) · 2020Review
- The role of natural products in revealing NRF2 function.Natural product reports · 2020Review
- Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner.Oxidative medicine and cellular longevity · 2020Article
- Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC.Frontiers in oncology · 2020Article
- Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis.Cell proliferation · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5-6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1 h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h later; their livers were harvested and serum collected for analysis. At 4 h, compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels, hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated mice, livers from WA-treated mice had reduced APAP-induced JNK activation, mitochondrial Bax translocation, and nitrotyrosine generation. Compared to vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1β. The hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of Il-6, Tnf-α and Il-1β, increased hepatic Gclc and Nqo1 expression and GSH levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced H₂O₂-induced oxidative stress and necrosis by preventing GSH depletion. Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte injury, and demonstrate that WA has therapeutic potential in AILI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.