基于网络药理学和动物实验探讨蓝杖颗粒改善代谢相关脂肪性肝病效应机制OA

Objective To investigate the mechanism of Lanzhang Granules in treating metabolic dysfunction-associated steatotic liver disease(MASLD)via network pharmacology and animal experiment.Methods Active components and molecular targets of Lanzhang Granules were retrieved using TCMSP.MASLD related targets were obtained through GeneCards and OMIM databases,and the drug component targets and disease targets were intersected.GO functional annotation and KEGG pathway enrichment of targets were performed via DAVID.The Chinese materia medica-active components-targets network and protein-protein interaction network were constructed to screen main active components and core targets.Molecular docking of key components with core targets was performed using AutoDock Vina and PyMOL.Lanzhang Granules was used to intervene MASLD model rats.The body weight,liver weight,blood lipid,aminotransferase were detected;liver morphology was observed;mRNA and protein expressions of core targets in liver tissue were detected by RT-qPCR and Western blot.Results Pelargonidin,jaranol,marin and 3,9-di-O-methylnissolin were identified as active components.Totally 210 MASLD-related targets were obtained,including AKT1,IL6,STAT3,PPARG,TP53.KEGG pathway enrichment highlighted glycolipid metabolism,inflammation and stress response,and apoptosis pathways.Molecular docking confirmed strong binding affinity between main active components and core targets.Animal experiments showed Lanzhang Granules significantly reduced body weight,liver weight,serum contents of TC,LDL-C,ALT and AST(P<0.05,P<0.01),improved hepatic steatosis and inflammation,and decreased TC and TG contents in liver tissue of model rats.It reversed mRNA expressions of IL-1,IL-6,TNF,PPARG,JUN,BAX and protein expressions of STAT3,P-JNK/JNK,P-NF-κB/NF-κB in liver tissue,which were up-regulated by model rats(P<0.05,P<0.01),while elevating BCL-2 mRNA expression and P-AKT/AKT protein expression,which were down-regulated by model rats(P<0.01).Conclusion Lanzhang Granules can improve glucose and lipid metabolism,inflammatory stress and cell apoptosis by regulating AKT1,IL6,STAT3,PPARG and other targets,which is the possible mechanism of improving MASLD.