中药新药与临床药理2025，Vol.36Issue(6)：918-928,11.DOI:10.19378/j.issn.1003-9783.2025.06.009
基于网络药理学和实验验证探讨清肝化痰方治疗代谢综合征的作用机制
Exploring the Mechanism of Qinggan Huatan Formula in Treating Metabolic Syndrome Based on Network Pharmacology and Experimental Validation
摘要
Abstract
Objective To explore the mechanism of Qinggan Huatan Formula in treating metabolic syndrome(MetS)based on network pharmacology and experimental validation.Methods(1)The active components of Qinggan Huatan Formula and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).MetS-related targets were retrieved from GeneCards,OMI,TTD,PharmGkb,and DrugBank databases.The intersection of drug-active component-target and disease-related targets was obtained using the Venny 2.1 platform to identify potential therapeutic targets of Qinggan Huatan Formula for MetS.A"drugs-active components-targets"network was constructed,and the common-target were imported into the STRING database to obtain protein-protein interaction(PPI)networks,identifying key active components and core targets of Qinggan Huatan Formula for MetS.GO functional and KEGG pathway enrichment analyses of common targets were performed using the Metascape database.(2)A MetS model was established by feeding C57BL/6J mice a high-fat diet.Forty mice were randomly divided into five groups:control group,model group,low-dose Qinggan Huatan Formula group(7.28 g·kg-1),medium-dose Qinggan Huatan Formula group(14.56 g·kg-1),and high-dose Qinggan Huatan Formula group(29.12 g·kg-1),with eight mice in each group.The mice were administered the formula by gavage once daily for four weeks.Insulin tolerance test(ITT)and pyruvate tolerance test(PTT)were used to assess ketone metabolism and insulin sensitivity.Serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using assay kits.Serum levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were detected by ELISA.The mRNA expression of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),IL-1β,TNF-α,and IL-6 in liver tissues was measured by RT-qPCR.Results(1)A total of 532 potential therapeutic targets of Qinggan Huatan Formula for MetS were identified.The top six active components were formic acid,quercetin,kaempferol,glycine,oxalic acid,and succinic acid.Core targets included PIK3CA,Akt1,EGFR,CCND1,SRC,and MAPK3.GO functional and KEGG pathway enrichment analyses revealed that these targets were mainly involved in processes such as response to nutrient levels,response to steroid hormones,and response to oxygen levels,with therapeutic mechanisms involving pathways such as PI3K/Akt.(2)Compared with the control group,the model group showed significantly increased fasting blood glucose,serum TNF-α,IL-6,IL-1β,TG,TC,LDL-C levels,and liver tissue TNF-α,IL-1β,IL-6,PI3K and Akt mRNA expression(P＜0.05,P＜0.01),increased area under the curve(AUC)of ITT and PTT(P＜0.05,P＜0.01),and decreased serum HDL-C levels(P＜0.05,P＜0.01).Compared with the model group,the Qinggan Huatan Formula treatment groups showed significantly reduced fasting blood glucose,serum TNF-α,IL-6,IL-1β,TG,TC,LDL-C levels,and TNF-α,IL-1β,IL-6,PI3K and Akt mRNA expression in liver tissue(P＜0.05,P＜0.01),decreased AUC of ITT and PTT(P＜0.05,P＜0.01),and increased serum HDL-C levels(P＜0.05,P＜0.01).Conclusion Components of Qinggan Huatan Formula,such as formic acid,quercetin,kaempferol,glycine,oxalic acid,and succinic acid,may improve hepatic inflammation and glucose-lipid metabolism disorders in MetS mice by regulating the PI3K/Akt signaling pathway,thereby exerting preventive and therapeutic effects on MetS.关键词
清肝化痰方/代谢综合征/网络药理学/糖脂代谢紊乱/实验验证/小鼠Key words
Qinggan Huatan Formula/metabolic syndrome/network pharmacology/glucose-lipid metabolism disorder/experimental verification/mice分类
医药卫生引用本文复制引用
刘思奇,苗得雨,邓靖于,李雅仪,张灿,沈创鹏..基于网络药理学和实验验证探讨清肝化痰方治疗代谢综合征的作用机制[J].中药新药与临床药理,2025,36(6):918-928,11.基金项目
国家自然科学基金项目(82160891). （82160891）
