The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro- and anti-inflammatory cytokines in rats with hepatic fibrosis

摘要

This study was designed to investigate the protective effects of Acanthus ilicifolius alkaloid A [4-hydroxy-2-benzoxazolone (HBOA)] and its acetylated derivatives including 4-acetoxy-2-benzoxazolone (TC-2) and 3-acetyl-4-acetoxy-2-benzoxazolone (TC-3) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Sprague-Dawley rats were given CCl4 twice per week for 8 weeks to induce liver fibrosis. Then, they were treated with HBOA, TC-2, and TC-3 daily for 4 weeks, respectively. The serum indicators including total protein (TP), albumin (Alb), globulin, hyaluronic acid (HA), and laminin (LN) were measured by commercial kits. The messenger ribonucleic acid expression of adiponectin, peroxisome proliferator-activated receptor- (PPAR-), tumor necrosis factor- (TNF-), interleukin-6 (IL-6), transforming growth factor-(1) (TGF-(1)) and Toll-like receptor 4 (TLR4) was determined by reverse-transcriptase -PCR. The proteins of adiponectin, TGF-(1), -smooth muscle actin (-SMA), and TLR4 were also detected by the immunohistochemical assay. The results showed that HBOA, TC-2, and TC-3 significantly attenuated the fibrotic degree induced by CCl4 as evidenced by higher levels of TP, Alb, adiponectin, and PPAR-, which in turn decreased the proliferation of hepatic stellate cells. Moreover, those drugs markedly decreased the levels of HA, LN, TNF-, IL-6, TGF-(1), -SMA, and TLR4. Our study indicates that HBOA, TC-2, and TC-3 have beneficial effects against liver fibrosis, and the mechanisms may be related to the inhibition of inflammatory response.