Anti-hepatic fibrotic mechanism of Acanthus ilicifolius alkaloid A involved in high mobility group box 1 / 中国药理学通报

ABSTRACT

Aim To investigate anti-hepatic fibrotic mechanism of Acanthus ilicifolius alkaloid A ( HBOA ) involved in high mobility group box 1 ( HMGB1 ) . Methods A hepatic fibrosis model of rat was estab-lished by the olive oil of CCl4 for 12 weeks. Then, at the 8th week,the successful model rats were randomly divided into model control group, colchicine group, HBOA high-dose group and HBOA low-dose group. From the 9th week,the rats in each group were treated with the drugs daily for 4 weeks respectively. The changes of liver histopathology and collagen were ob-served by HE staining and Masson staining, and the serum indicators including aspartate aminotransferase (AST),alanine aminotransferase(ALT) , total biliru-bin ( T-BIL ) , HMGB1 , interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were determined. Moreover , the protein of HMGB1 in liver was examined by immunohistochemistry, and the expression of HMGB1 mRNA was measured by real-time fluores-cence quantitative PCR. Results Compared with the model control group,HBOA high-dose and HBOA low-dose groups significantly attenuated the fibrotic degree induced by CCl4 , markedly decreased the levels of ALT, AST, T-BIL, HMGB1, IL-1β, TNF-α. Moreo-ver, the expression of HMGB1 protein and mRNA in liver was decreased. And furthermore, serum HMGB1 level had significant positive correlation with IL-1β, TNF-α,ALT,AST and T-BIL. Conclusion HBOA has beneficial effects against liver fibrosis in rat which is induced by CCl4 , the mechanisms may be related to the inhibition of inflammatory response to HMGB1 .