Abstract
Evodia rutaecarpa (E.R.) is a commonly used Chinese herbal medicine. However, it exerts certain hepatotoxicity and the underlying molecular mechanism has not been clarified. In this study, we investigated the molecular mechanism involved in hepatotoxicity induced by E.R. Mice were treated with E.R. water- and ethanol-extract at dosage equivalent to 16.67 g crude-drug/kg body weight by intragastric administration once a day on 30 consecutive days. The effect of E.R. extract on liver, manifested by histopathologic effects, liver index, and blood biochemical indexes were tested. In addition, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in liver tissue were measured. The signaling transduction molecules were determined by antibody microarray assay, and verified by western blot. E.R. extract, either water- or ethanol-extract, can induce liver dysfunction. Signaling molecules, Erk1/2, Src, CDK8 and CK1e, were involved in this process. E.R. extract can induce Ck1e expression and phosphorylation of Erk1/2 and CDK8, and inhibit Src phosphorylation. Inflammatory cytokines in liver tissue, IL-1β, IL-6, IL-8, and TNF-α were markedly increased upon the treatment of E.R. extract. In conclusion, E.R.-induced hepatotoxicity was due to the expression of inflammatory cytokine, which was mediated through Erk1/2, Src, CDK8 and CK1e.
Highlights
Evodia rutaecarpa (E.R.), first recorded in the ancient medicine book of “Shen Nong’s Herbal” with functions of smoothing liver and analgesia, is the dry mature fruit harvested from perfume plants, such as E.R. (Juss) Benth
The liver index was significantly increased in the E.R. water-extract and ethanol-extract groups compared with the control group
The serum parameters related to liver function, alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), total cholesterol (TC) and glucose (GLU) were measured
Summary
Evodia rutaecarpa (E.R.), first recorded in the ancient medicine book of “Shen Nong’s Herbal” with functions of smoothing liver and analgesia, is the dry mature fruit harvested from perfume plants, such as E.R. (Juss) Benth. Evodia rutaecarpa (E.R.), first recorded in the ancient medicine book of “Shen Nong’s Herbal” with functions of smoothing liver and analgesia, is the dry mature fruit harvested from perfume plants, such as E.R. E.R. is a commonly used Chinese herbal medicine and exerts many beneficial effects, such as analgesia through either inhibition of COX2 or desensitizing sensory nerves [1] [2] and cardiovascular and gastrointestinal protection through either activation of cholecystokinin 1 receptor or transient receptor potential channel vanilloid type 1 [3] [4]. Toxicity of E.R., especially hepatotoxicity, has been found recently [5] [6]. We found that either water- or ethanol-extracts of E.R. could increase the liver index, serum total cholesterol and glutamic-pyruvic transaminase in rats in a dose-dependent manner. The molecular mechanism involved in the E.R.-induced hepatotoxicity has not been clarified yet
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
