BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently available.Yinhuang granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Loni...BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently available.Yinhuang granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos.It is frequently used for upper respiratory tract infections,pharyngitis,as well as acute and chronic tonsillitis.AIM To investigate the potential of YHG in alleviating carbon tetrachloride(CCl4)-induced liver fibrosis in mice.METHODS To induce a hepatic fibrosis model in mice,this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk.Meanwhile,liver fibrosis mice in the low dose of YHG(0.4 g/kg)and high dose of YHG(0.8 g/kg)groups were orally administered YHG once a day for 4 wk.Serum alanine/aspartate aminotransferase(ALT/AST)activity and liver hydroxyproline content were detected.Sirius red and Masson's trichrome staining assay were conducted.Realtime polymerase chain reaction,western-blot and enzyme-linked immunosorbent assay were conducted.Liver glutathione content,superoxide dismutase activity level,reactive oxygen species and protein carbonylation amount were detected.RESULTS The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice,as reflected by decreased serum ALT/AST activity and improved liver histological evaluation.YHG also attenuated liver fibrosis,evident through reduced liver hydroxyproline content,improvements in Sirius red and Masson's trichrome staining,and lowered serum hyaluronic acid levels.Furthermore,YHG hindered the activation of hepatic stellate cells(HSCs)and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice.YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2(Nrf2)and upregulated the expression of Nrf2-dependent downstream antioxidant genes.In addition,YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice,as demonstrated by increased liver adenosine triphosphate content,mitochondrial DNA levels,and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.CONCLUSION YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs,reducing inflammation,alleviating liver oxidative stress damage through Nrf2 activation,and promoting liver mitochondrial biogenesis.展开更多
基金Supported by Preclinical Study of A New Chinese Herbal Medicine for the Treatment of Ascites of Liver Cirrhosis(Spleen and Kidney Yang Deficiency Type)with the Clinical Formula of Qigui Xiaogu Cataplasm,No.23S21900100Traditional Chinese Medicine/Chinese and Western Medicine Advantage Specialty Construction Specialty for Department of Hepatology,No.YW(2023-2024)-01-03+2 种基金National Natural Science Foundation of China,No 82074386Construction of Special Disease Alliance of Traditional Chinese Medicine in East China Area and Municipal Level,Shanghai Special Disease Alliance of Traditional Chinese Medicine for Liver Cirrhosis Ascites(Water sickness),and Clinical Research Plan of SHDC,No.SHDC2020CR3095BNational Funded Postdoctoral Researcher Program,No.GZB20230448.
文摘BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently available.Yinhuang granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos.It is frequently used for upper respiratory tract infections,pharyngitis,as well as acute and chronic tonsillitis.AIM To investigate the potential of YHG in alleviating carbon tetrachloride(CCl4)-induced liver fibrosis in mice.METHODS To induce a hepatic fibrosis model in mice,this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk.Meanwhile,liver fibrosis mice in the low dose of YHG(0.4 g/kg)and high dose of YHG(0.8 g/kg)groups were orally administered YHG once a day for 4 wk.Serum alanine/aspartate aminotransferase(ALT/AST)activity and liver hydroxyproline content were detected.Sirius red and Masson's trichrome staining assay were conducted.Realtime polymerase chain reaction,western-blot and enzyme-linked immunosorbent assay were conducted.Liver glutathione content,superoxide dismutase activity level,reactive oxygen species and protein carbonylation amount were detected.RESULTS The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice,as reflected by decreased serum ALT/AST activity and improved liver histological evaluation.YHG also attenuated liver fibrosis,evident through reduced liver hydroxyproline content,improvements in Sirius red and Masson's trichrome staining,and lowered serum hyaluronic acid levels.Furthermore,YHG hindered the activation of hepatic stellate cells(HSCs)and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice.YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2(Nrf2)and upregulated the expression of Nrf2-dependent downstream antioxidant genes.In addition,YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice,as demonstrated by increased liver adenosine triphosphate content,mitochondrial DNA levels,and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.CONCLUSION YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs,reducing inflammation,alleviating liver oxidative stress damage through Nrf2 activation,and promoting liver mitochondrial biogenesis.
