Oxymatrine Induces Liver Injury through JNK Signalling Pathway Mediated by TNF‐α In Vivo

Abstract Oxymatrine ( OMT ) is a traditional Chinese medicine monomer and has been used for the treatment of chronic viral hepatitis and many other diseases. We aimed to investigate whether OMT could induce hepatotoxicity in mice and explored the preliminary mechanisms of toxic effects. Twenty‐four Institute for Cancer Research male mice were randomly divided into four groups: control group, 40, 160 and 320 mg/kg OMT ‐treated group. OMT was orally administered once daily for 7 days. The OMT ‐treated group exhibited an improved liver index and increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase,augmented liver histological injury, elevated levels of malondialdehyde and tumour necrosis factor alpha ( TNF ‐α) accompanied by the activation of caspase‐9/‐8/‐3, up‐regulated expressions of tumour necrosis factor receptor l ( TNFR 1), TNF receptor‐associated structure domain ( TRADD ) and phosphorylation of stress‐activated protein kinase/c‐jun N‐terminal protein kinases (p‐ SAPK / JNK ). Altogether, these results suggest that OMT at a dose of 320 mg/kg leads to liver damage and is related to the activation of JNK signalling pathway mediated by TNF ‐α in the liver of mice.