Liver fibrosis is a pathological process characterized by excess deposition of extracellular matrix(ECM)that are mainly derived from activated hepatic stellate cells.Previous studies suggested that ligustroflavone(LF)...Liver fibrosis is a pathological process characterized by excess deposition of extracellular matrix(ECM)that are mainly derived from activated hepatic stellate cells.Previous studies suggested that ligustroflavone(LF)was an ingredient of Ligustrum lucidum Ait.with activities of anti-inflammation and anti-oxidation.In this study,we investigated whether LF had any effect on liver fibrosis.In our study,we established a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis and used TGF-β1-stimulated human hepatic stellate cell line(LX-2)to explore the effect of LF and associated underlying mechanism.LF was used in vivo with low dose(L-LF,5 mg·kg^(-1),i.p.,3 times each week)and high dose(H-LF,20 mg·kg^(-1),i.p.,3 times each week)and in vitro(25μmol·L^(-1)).Histopathological and biochemical assays investigations showed that LF delayed the formation of liver fibrosis;decreased AST,ALT activities and increased Alb activity in serum;decreased MDA level,Hyp content and increased GSH-Px concentration,SOD activity in liver tissues.Moreover,immunohistochemical,immunofluorescent and Western blot results showed that LF reduced the expressions of hepatic stellate cells specific marker proteins,including collagen I andα-SMA in vivo and in vitro.In addition,LF markedly suppressed TGF-β1-upregulated protein expressions of TβR I,TβR II,P-Smad2,P-Smad3 and Smad4 in LX-2 cells.Taken together,these findings demonstrated LF could decrease histopathological lesions,ameliorate oxidative injury,attenuate CCl4-induced liver fibrosis,which may be associated with down-regulating the TGF-β/Smad signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81770432 and 81970245)the Science and Technology Program of Shaanxi Province,China(Nos.2019PT-23 and 2019ZDLSF04-03-01)。
文摘Liver fibrosis is a pathological process characterized by excess deposition of extracellular matrix(ECM)that are mainly derived from activated hepatic stellate cells.Previous studies suggested that ligustroflavone(LF)was an ingredient of Ligustrum lucidum Ait.with activities of anti-inflammation and anti-oxidation.In this study,we investigated whether LF had any effect on liver fibrosis.In our study,we established a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis and used TGF-β1-stimulated human hepatic stellate cell line(LX-2)to explore the effect of LF and associated underlying mechanism.LF was used in vivo with low dose(L-LF,5 mg·kg^(-1),i.p.,3 times each week)and high dose(H-LF,20 mg·kg^(-1),i.p.,3 times each week)and in vitro(25μmol·L^(-1)).Histopathological and biochemical assays investigations showed that LF delayed the formation of liver fibrosis;decreased AST,ALT activities and increased Alb activity in serum;decreased MDA level,Hyp content and increased GSH-Px concentration,SOD activity in liver tissues.Moreover,immunohistochemical,immunofluorescent and Western blot results showed that LF reduced the expressions of hepatic stellate cells specific marker proteins,including collagen I andα-SMA in vivo and in vitro.In addition,LF markedly suppressed TGF-β1-upregulated protein expressions of TβR I,TβR II,P-Smad2,P-Smad3 and Smad4 in LX-2 cells.Taken together,these findings demonstrated LF could decrease histopathological lesions,ameliorate oxidative injury,attenuate CCl4-induced liver fibrosis,which may be associated with down-regulating the TGF-β/Smad signaling pathway.
