Efficacy of Ganshuang granules(肝爽颗粒)on non-alcoholic fatty liver and underlying mechanism:a network pharmacology and experimental verification

OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-αin the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

Effect of entecavir plus Ganshuang granule(肝爽颗粒) on fibrosisand cirrhosis in patients with chronic hepatitis B

OBJECTIVE:To investigate the effect of entecavir plus Ganshuang granule(肝爽颗粒,GSG)on advanced fibrosis and cirrhosis in patients with chronic hepatitis B virus infection.METHODS:One hundred thirty-five patients were randomly assigned to one of two cohorts:GSG cohort(n=69)or placebo cohort(n=66).The GSG cohort received entecavir plus GSG and the placebo cohort received entecavir plus placebo for 48 weeks.Liver biopsy was performed at baseline and between weeks 44 and 48 during this placebo-controlled trial.We assessed histological improvement(greater than a two-point decrease using the Knodell in fl ammatory score and no worsening of the Ishak fibrosis score)and fibrosis regression(a decrease of at least one point in the Ishak fibrosis score).RESULTS:There were 95.7% of patients(66/69)in the GSG cohort and 66.7%(44/66)of patients in the placebo cohort who showed necroin t.The mean reduction in flth ammation improvemene Knodell necroinflammatory score was 5.1 and 2.6,respectively.There were 89.9%(62/69)of patients in the GSG cohort and 31.8%(21/66)of patients in the placebo cohort who showed at least a one-point improvement in the Ishak fibrosis score.The mean reduction in the Ishak fibrosis score was 1.7 and 0.4,respectively.CONCLUSION:Patients with advanced fibrosis and cirrhosis caused by chronic hepatitis B showed more improvement in liver histology in a shorter time after treatment with entecavir plus GSG compared with entecavir plus placebo.