Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease / 中国药房

ABSTRACT

OBJECTIVE To investigate the intervention effect and mechanism of Wuwei baogan pill on mice with non- alcoholic fatty liver disease （NAFLD）. METHODS The mice were given high-fat and high-sugar diet for 19 weeks to induce NAFLD model. The model mice were randomly grouped into model group， positive control group （polyene phosphatidylcholine capsules， 23.30 mg/kg）， Wuwei baogan pill low-dose， medium-dose and high-dose groups （0.11， 0.23， 0.45 g/kg）， with 8 mice in each group； the normal group was additionally set up without modeling. Administration groups were given relevant medicine intragastrically， and model group and normal group were given constant volume of normal saline， once a day， for consecutive 4 weeks. After the last administration， glucose metabolism （including fasting blood glucose， fasting insulin， insulin resistance index）， liver function [liver index， alanine aminotransferase （ALT）， aspartate aminotransferase （AST），liver tissue pathological score]， lipid metabolism [triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high- density lipoprotein cholesterol （HDL-C）] were measured； the pathological morphology of liver tissue， as well as fibrosis， lipid droplet formation， and glycogen synthesis were observed； the levels of free fatty acid （FFA） in serum and inflammatory factors in liver tissue [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β] were detected； the expressions of insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B/ glycogen synthase kinase 3β （IRS/PI3K/AKT/GSK3β） signaling pathway-related protein in liver tissue were investigated. RESULTS After intervention with high-dose Wuwei baogan pill， liver index of NAFLD mice， serum levels of ALT， AST， FFA， TC， TG and LDL-C， the levels of TNF-α， IL-6 and IL-1β in liver tissue， fasting blood glucose， fasting insulin， insulin resistance index， liver tissue pathological score， proportions of fibrotic staining area and lipid droplet staining area all significantly decreased （P＜0.05）； the level of HDL-C， proportion of glycogen staining area， the phosphorylation of IRS1， PI3K， AKT and GSK3β protein increased significantly （P＜0.05）； the degree of liver cell necrosis and steatosis was reduced， and the fibrotic lesions were alleviated. The above indexes of mice were improved in Wuwei baogan pill low-dose and medium-dose groups， but there was no statistically significant difference in some indexes. CONCLUSIONS Wuwei baogan pill can regulate lipid and glucose metabolism disorders in the liver of NAFLD mice， and improve liver injury， the mechanism of which may be associated with the activation of IRS/PI3K/AKT/GSK3β signaling pathway.