ArticleChemical research in toxicology2014
Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice.
Article in Chemical research in toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- Review
- AB-Free Kava and Dihydromethysticin Inhibit Chronic Hexavalent Chromium Exposure-Induced Cell Malignant Transformation through Down-Regulating RNA Splicing Factor SNRPA1 Expression.Chemical research in toxicology · 2026Article
- Multi-target therapeutic potential of Flavokawain A in rheumatoid arthritis: A mechanistic and translational perspective.Inflammopharmacology · 2026Review
- Kava (Piper methysticum) consumption patterns and conceptualizations: results from an online survey.Substance abuse treatment, prevention, and policy · 2026Article
- Amide linked chalcone derivatives, a promising class of compounds with versatile biological effects.RSC advances · 2025Review
- The potential of AB-free kava in enabling tobacco cessation via management of abstinence-related stress and insomnia: study protocol for a randomized clinical trial.BMC complementary medicine and therapies · 2024Article
- Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice.ACS pharmacology & translational science · 2024Article
- Opportunities and Challenges of Kava in Lung Cancer Prevention.International journal of molecular sciences · 2023Review
- Reducing tobacco-associated lung cancer risk: a study protocol for a randomized clinical trial of AB-free kava.Trials · 2023Article
- Dietary Phytochemicals as Potential Chemopreventive Agents against Tobacco-Induced Lung Carcinogenesis.Nutrients · 2023Review
- Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers.Journal of ethnopharmacology · 2022Article
- Medicinal Plants Used for Anxiety, Depression, or Stress Treatment: An Update.Molecules (Basel, Switzerland) · 2022Review
- An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava.Journal of clinical medicine · 2022Review
- Chalcone Derivatives: Role in Anticancer Therapy.Biomolecules · 2021Review
- Article
- Kava as a Clinical Nutrient: Promises and Challenges.Nutrients · 2020Review
- The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Improving natural product research translation: From source to clinical trial.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer.Oncology letters · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its beneficial applications. In this study we evaluated the toxicity of kava as a single entity or in combination with acetaminophen (APAP) in C57BL/6 mice. Kava alone revealed no adverse effects for long-term usage even at a dose of 500 mg/kg bodyweight. On the contrary a three-day kava pretreatment potentiated APAP-induced hepatotoxicity, resulted in an increase in serum ALT and AST, and increased severity of liver lesions. Chalcone-based flavokawains A (FKA) and B (FKB) in kava recapitulated its hepatotoxic synergism with APAP while dihydromethysticin (DHM, a representative kavalactone and a potential lung cancer chemopreventive agent) had no such effect. These results, for the first time, demonstrate the hepatotoxic risk of kava and its chalcone-based FKA and FKB in vivo and suggest that herb-drug interaction may account for the rare hepatotoxicity associated with anxiolytic kava usage in humans.
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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.