复方柏芪丸调控PI3K/AKT/FOXO1通路改善代谢综合征大鼠糖脂代谢紊乱的作用机制研究OA

Objective:To investigate the mechanisms through which Compound Boqi(柏芪)Pills ameliorate glu-cose and lipid metabolism disorders in the rat model of metabolic syndrome(MS)based on in vivo pharmacodynamic ex-periments and network pharmacology.Methods:Network pharmacology was employed to predict the potential targets and signaling pathways of Compound Boqi Pills in ameliorating glucose and lipid metabolism disorders.A rat model of MS characterized primarily by glucose and lipid metabolism disorders was established via a high-sugar,high-fat diet combined with streptozotocin(STZ)injection.The successfully modeled rats were randomized into the following groups:model con-trol,Compound Boqi Pills(0.6,1.3,and 2.5 g/kg),Xuezhikang(0.1 g/kg),and metformin(0.2 g/kg).After 6 con-secutive weeks of administration,fasting blood glucose(FBG)was measured.Serum levels of insulin(INS),total cho-lesterol(TC),triglycerides(TG),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were deter-mined.Hepatic levels of superoxide dismutase(SOD),reduced glutathione(GSH),and malondialdehyde(MDA)were assessed.Histopathological changes in the liver and pancreas tissue were examined by hematoxylin-eosin(HE)staining,and hepatic lipid droplets were detected by oil red O staining.Key signaling pathways were ultimately validated by RT-qPCR and immunohistochemical staining.Results:Network pharmacology analysis identified 75 active components in-volved in the amelioration of glucose and lipid metabolism disorders by Compound Boqi Pills,which acted on 200 poten-tial targets.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indicated that the main pathways involved included the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway,the mitogen-ac-tivated protein kinase(MAPK)signaling pathway,and the advanced glycation end products(AGEs)and their receptor(RAGE)signaling pathway associated with diabetic complications.Animal experiments demonstrated that Compound Bo-qi Pills lowered the FBG and alleviated glucose tolerance,insulin resistance,dyslipidemia,liver function damage,liver lipid deposition,and oxidative stress in the rat model of MS.Mechanism verification showed that Compound Boqi Pills could up-regulate the mRNA levels of Pi3k and Akt,down-regulate the mRNA level of forkhead box protein O1(Foxo1),and increase the positive expression areas of p-PI3K,p-AKT,and p-FOXO1 in the liver tissue.Conclusion:Compound Boqi Pills can ameliorate the glucose and lipid metabolism disorder in the rat model of MS induced by a high-sugar and high-fat diet combined with STZ by enhancing PI3K/AKT signaling,promoting FOXO1 phosphorylation inactivation,and reducing liver oxidative stress and inflammatory damage.