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 isochlo...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.展开更多
OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related fa...OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.展开更多
OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug...OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer.Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications.Naringenin(NGN)is a flavonoid compound rich in citrus fruits.Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver,but whether NGN can attenuate liver fibrosis of NASH is not known.METHODS To study the effect of NGN on NASH fibrosis.WT mice were fed with high fat diet(HFD)and injected intraperitoneally 20%carbon tetrachloride at the same time for 8 weeks to induce NASH,and NGN was administrated by gavage in the meantime.In vitro,LO2 cells and LX2 cells were stimulated by oleic acid(OA)combined with lipopolysaccharide(LPS),respectively.RESULTS Treating the WT mice with NGN 100 mg·kg^(-1)·d-1 significantly attenuated hepatic lipid accumulation,hepatic fibrosis,plasma ALT and AST levels,inhibited protein expression of p-ERK,p-FoxO3a in the mouse livers.In vitro,on OA and LPS stimulated LO2 or LX2 cells,NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes.Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a,consequently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis.CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway,thus promoting apoptosis of the activated hepatic stellate cells.展开更多
文摘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.
文摘OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.
文摘OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis(NASH)include liver steatosis,inflammation,and fibrosis.Fibrosis is the most severe and significant pathological feature in NASH.Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer.Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications.Naringenin(NGN)is a flavonoid compound rich in citrus fruits.Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver,but whether NGN can attenuate liver fibrosis of NASH is not known.METHODS To study the effect of NGN on NASH fibrosis.WT mice were fed with high fat diet(HFD)and injected intraperitoneally 20%carbon tetrachloride at the same time for 8 weeks to induce NASH,and NGN was administrated by gavage in the meantime.In vitro,LO2 cells and LX2 cells were stimulated by oleic acid(OA)combined with lipopolysaccharide(LPS),respectively.RESULTS Treating the WT mice with NGN 100 mg·kg^(-1)·d-1 significantly attenuated hepatic lipid accumulation,hepatic fibrosis,plasma ALT and AST levels,inhibited protein expression of p-ERK,p-FoxO3a in the mouse livers.In vitro,on OA and LPS stimulated LO2 or LX2 cells,NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes.Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a,consequently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis.CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway,thus promoting apoptosis of the activated hepatic stellate cells.
