Cirsium japonicum var. ussuriense extract and cirsimaritin prevents the expressions of IL-17 in high-fat diet induced non-alcoholic steatohepatitis

Abstract

Abstract Nonalcoholic fatty liver disease (NAFLD) corresponds to hepatic manifestations of inflammation and accumulations of fatty acids in the liver. Recently, IL-17 signaling pathways have been shown to contribute to the pathogenesis of NAFLD. Cirsium japonicum var. ussuriense is often used in treatment of human diseases such as hemorrhage, blood congestion and inflammation. Despite the known biological activities of C. japonicum var. ussuriense, its effect on NAFLD is still unknown. Here, we investigated the effects of C. japonicum var. ussuriense extract (CJE) and cirsimaritin, its main constituents, on high-fat diet (HFD) or oleic acid (OA)-induced IL-17 expressions associated with steatohepatitis. We found that the levels of IL-17 was reduced in OA-treated HepG2 cells and in mice fed with HFD and administered with CJE and cirsimaritin at the mRNA, protein, and serum expression levels. Further investigation showed that CJE and cirsimaritin suppressed MAPK and NF-κB, the key signaling pathway responsible for IL-17 expression in HFD-fed mice and OA-treated hepatocytes, thus suggesting that the action of CJE and cirsimaritin on signaling molecules might have been responsible for the suppression of IL-17. Here, we also demonstrated that administration of CJE and cirsimaritin reduced triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels in OA-treated HepG2 cells; and protected mice against HFD-induced triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels. The results collectively demonstrate that CJE and cirsimaritin may protect against IL-17 exacerbated HFD-induced steatohepatitis.