中药药理与临床2025，Vol.41Issue(3)：2-9,8.
基于网络药理学及实验验证探讨大柴胡汤抗非酒精性脂肪性肝病的作用机制
Mechanism of DaChaiHu(大柴胡)Decoction against Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Validation
摘要
Abstract
Objective:To explore the mechanism of action of DaChaiHu(大柴胡)Decoction in the treatment of non-alcoholic fatty liver disease(NAFLD)by using network pharmacology and molecular docking methods,and to validate these findings through animal experiments.Meth-ods:The active ingredients and targets of DaChaiHu Decoction were collected and screened by using the TCMSP and SwissTargetPrediction databases.Disease targets related to NAFLD were obtained from GeneCards,DrugBank,DisGeNET,OMIM,and TTD databases,and drug-dis-ease intersecting targets were identified.The"drug-active ingredient-target"network and protein-protein interaction(PPI)network were con-structed using Cytoscape 3.9.1 software to further screen core active ingredients and targets.Gene ontology(GO)function and Kyoto ency-clopedia of genes and genomes(KEGG)pathway enrichment analyses of the intersecting targets were performed by using the Metascape data-base.Molecular docking was conducted to verify the core active ingredients and targets of DaChaiHu Decoction in the treatment of NAFLD.A high-fat diet-induced NAFLD mouse model was established,and the network pharmacology prediction results were validated through animal ex-periments.Results:Network pharmacology predicted 90 potential target genes for DaChaiHu Decoction in the treatment of NAFLD,including TNF,IL6,IL1B,TP53,and PPARG.The core active ingredients identified were protoporphyrin,(E)-11-gondoic acid,10,13-eicosadienoic acid,epiberberine,mauritine D,and kaempferol.GO function enrichment analysis showed significant enrichment in biological processes such as response to bacterial molecules,positive regulation of small molecule metabolic processes,and regulation of secretion,in cellular compo-nents such as membrane rafts,receptor complexes,and cytoplasmic perinuclear regions,and in molecular functions such as nuclear receptor activity,monocarboxylic acid binding,and protein domain-specific binding.KEGG pathway enrichment analysis indicated that DaChaiHu De-coction exerted anti-NAFLD effects by modulating peroxisome proliferator-activated receptor(PPAR)and other signalling pathways.Molecu-lar docking results demonstrated that the core active ingredients had strong binding activity with the core targets.Animal experiments showed that DaChaiHu Decoction effectively reduced lipid levels,oxidative stress,and inflammatory factors in NAFLD mouse models.It decreased se-rum contents of TG,TC,and LDL-C(P<0.05 or P<0.01),serum AST and ALT activities(P<0.05 or P<0.01),liver MDA level(P<0.01),and contents of TNF-α,IL-6,and IL-1β(P<0.05 or P<0.01)while increasing serum HDL-C levels(P<0.05)and liver SOD activi-ty(P<0.01).HE and Oil Red O staining results indicated that DaChaiHu Decoction effectively alleviated hepatic fatty degeneration,vacuolar lesions,and red lipid droplets in NAFLD mouse models.RT-qPCR results showed that DaChaiHu Decoction significantly down-regulated the mRNA expression levels of Tnfα,Il6,and Il1β in liver(P<0.05 or P<0.01)and up-regulated the mRNA expression levels of Pparγ,Akt1,and Ampk(P<0.05).Conclusion:DaChaiHu Decoction effectively reduces lipid deposition,oxidative stress,and inflammatory responses in NAFLD mice,improves liver function,and alleviates pathological damage.Its mechanism of action may be related to down-regulating the lev-els of TNF-α,IL-6,and IL-1β and regulating the PPARγ signalling pathway.关键词
大柴胡汤/非酒精性脂肪性肝病/网络药理学/分子对接/作用机制/蛋白激酶/过氧化物酶体增殖物激活受体/单磷酸腺苷蛋白激酶Key words
DaChaiHu(大柴胡)Decoction/Non-Alcoholic Fatty Liver Disease/Network Pharmacology/Molecular Docking/Mechanism of Action引用本文复制引用
钟光成,刘启华,麦灏铭,潘亚茹,李舒婷,杨虹颖,谢怀德,杨从,王奇..基于网络药理学及实验验证探讨大柴胡汤抗非酒精性脂肪性肝病的作用机制[J].中药药理与临床,2025,41(3):2-9,8.基金项目
国家自然科学基金面上项目(编号:82274616) （编号:82274616）
广东省基础与应用基础研究基金企业联合基金(编号:2022A1515220121). （编号:2022A1515220121）
