摘要
OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlorogenic acid A(ICQA)on liver fibrosis induced by carbon tetrachloride(CCl4)and clarify the underlying mechanism.METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10,20 and 40 mg·kg-1).RESULTS ICQA had significant protective effect on liver injury,inflammation,and fibrosis in rats.Meanwhile,ICQA prevented the activation of hepatic stellate cells(HSC)as indicated by inhibiting the overexpres⁃sion of a-smooth muscle actin(a-SMA).In addition,reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1)and toll like receptor(TLR)4.Moreover,ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver.Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB)p65 and inhibited degradation of IkBa expression in the liver of rats with liver fibrosis.CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.
OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available. This study aimed to investigate the effects of isochlorogenic acid A（ICQA） on liver fibrosis induced by carbon tetrachloride（CCl4） and clarify the underlying mechanism. METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10, 20 and 40 mg·kg-1). RESULTS ICQA had significant protective effect on liver injury, inflammation, and fibrosis in rats. Meanwhile, ICQA prevented the activation of hepatic stellate cells（HSC） as indicated by inhibiting the overexpression of a-smooth muscle actin（a-SMA）. In addition, reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1（HMGB1） and toll like receptor（TLR）4. Moreover, ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver. Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB（NF-κB） p65 and inhibited degradation of IkB a expression in the liver of rats with liver fibrosis. CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第9期692-692,共1页
Chinese Journal of Pharmacology and Toxicology
