The effect of ß-caryophyllene on nonalcoholic steatohepatitis.

ABSTRACT

The pathogenesis of nonalcoholic steatohepatitis (NASH) is not fully understood, but many studies have suggested that oxidative stress plays a key role. The methionine- and choline-deficient diet (MCD) administration model can reproduce histopathological features of human NASH and is widely used for investigating NASH. C57BL/6J mice have been used in many studies, but strain differences in pathogenesis have not been sufficiently investigated. We administred MCD to two mouse strains and then compared difference between strains and investigated the effects of ß-caryophyllene (BCP), which possesses an antioxidant effect, on development and progression of NASH. ICR and C57BL/6J mice were administred a control diet, MCD, MCD containing 0.02% BCP, or MCD containing 0.2% BCP. After 4 or 8 weeks, mice were sacrificed. In both strains, MCD administration induced hepatic steatosis and inflammation. These lesions were more severe in C57BL/6J mice than ICR mice, and liver fibrosis was observed at 8 weeks in C57BL/6J mice. These changes were attenuated by BCP coadministration. The mRNA expression of monocyte chemotactic and activating factor (MCP)-1 and fibrosis-related factors increased in C57BL/6J mice, and these increases were reduced by BCP coadministration. The mRNA expression of antioxidant-related factors decreased in both strains, and these decreases were attenuated by BCP coadministration. Based on these results, the C57BL/6J mouse was a more suitable model for MCD-induced NASH than the ICR mouse. In addition, it was suggested that antioxidant effect of BCP might suppressed the damage of hepatocytes caused by oxidative stress and following inflammation and fibrosis.