Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

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.

Quzhi Formula Alleviates Nonalcoholic Steatohepatitis by Impairing Hepatocyte Lipid Accumulation and Inflammation via Bip/eIF2α Signaling

Background and Aims:The Quzhi formula,a Chinese med-icine compound prescription,relieves nonalcoholic steato-hepatitis(NASH)symptoms.This study aimed to explore the mechanism of the Quzhi formula against NASH.Methods:A choline-deficient,L-amino acid-defined,high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro.Network pharmacol-ogy and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH.Key factors in liver lipid metabolism and endoplasmic reticulum(ER)stress pathway were evalu-ated to verify the mechanism.Results:The positive contri-bution of the Quzhi formula on NASH was confirmed in vivo and in vitro.Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula.Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses,which was enhanced by further molecular docking analy-sis.In addition,mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2αsignaling.Conclusions:The Quzhi formula protected against NASH by inhibiting lipid accumulation,ER stress,and inflammatory responses,which supports the potential use of Quzhi formula as an alternative treatment for NASH.