基于网络药理学和实验验证探讨侧柏双参方治疗雄激素性脱发的作用机制  

Exploring the mechanism of Cebai Shuangshen Formula in treating androgenic alopecia based on network pharmacology and experimental verification

作　　者：许佳 马旺明 宫恬 王萍 杨斌[5] 宋坪 XU Jia;MA Wangming;GONG Tian;WANG Ping;YANG Bin;SONG Ping(Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院皮肤科,北京100053 [2]江西中医药大学药学院 [3]沈阳药科大学中药学院 [4]中国中医科学院中药研究所 [5]中国中医科学院西苑医院病理科 [6]中国中医科学院西苑医院皮肤科

出　　处：《环球中医药》2025年第4期655-663,共9页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(82474521);北京中西医结合学会科研促进工作委员会科研课题(BJZXY-2024-YY0002)。

摘　　要：目的利用网络药理学和分子对接技术,探索侧柏双参方治疗雄激素性脱发(androgenetic alopecia,AGA)的潜在分子机制,并进行实验验证。方法运用GeneCards、OMIM数据库检索AGA靶点,利用TCMSP数据库收集侧柏叶、丹参、人参、吴茱萸的成分及靶点,筛选疾病和药物共有靶点,再通过STRING在线平台构建蛋白—蛋白互作(protein-protein interaction,PPI)网络,并构建中药—成分—靶点—通路网络图,采用DAVID数据库进行基因本体(gene ontology,GO)功能与京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,明确中药治疗AGA的核心靶点及潜在分子机制,运用AutoDockTools1.5.6软件对核心靶点与活性成分进行分子对接。将40只C57BL/6J小鼠随机分为空白组、模型组、米诺地尔组、组方高剂量组,每组各10只。除空白组外其余各组小鼠采用睾酮(5 mg/mL)外擦建立AGA小鼠模型,2小时后,米诺地尔组与组方高剂量组分别外涂5%米诺地尔溶液、200 mg/mL的组方溶液,连续干预16天。采用免疫印迹法检测造模部位皮肤组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)、p-Smad2、Smad2、p-Smad3、Smad3蛋白表达。结果获取AGA疾病靶点1118个,药物靶点299个,共有靶点185个,主要涉及TGF-β、Wnt等信号通路,分子对接显示主要成分与关键靶点结合活性良好。干预第16天,与模型组比较,米诺地尔组和组方高剂量组中TGF-β1表达、p-Smad2/Smad2以及p-Smads3/Smads3的比值降低(P<0.05)。结论侧柏双参方可能通过调节TGF-β信号通路发挥其在治疗AGA中的潜在疗效。Objective This study employs network pharmacology and molecular docking technologies to elucidate the underlying molecular mechanisms of Cebai Shuangshen Formula in the treatment of androgenetic alopecia(AGA),followed by experimental validation to confirm their therapeutic potential.Methods Employing GeneCards and OMIM databases to retrieve targets associated with AGA,utilizing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)to collect the components and targets of Platycladus orientalis(L.)Franco leaves,Salvia miltiorrhiza,Panax ginseng,and Evodia rutaecarpa,and screening for common disease and drug targets.Then,a protein-protein interaction(PPI)network was constructed through the STRING online platform,and a network diagram of traditional Chinese medicine components targets pathways was constructed.The DAVID database was used for gene ontology(GO)functional and Kyoto encyclopedia of genes and genomes(KEGG)metabolic pathway enrichment analysis to clarify the core targets and potential molecular mechanisms of traditional Chinese medicine treatment for AGA.Finally,the software AutoDockTools 1.5.6 was employed to conduct molecular docking studies between the key targets and the active constituents.Forty C57BL/6J mice were randomly divided into six groups:blank group,model group,minoxidil group,and high dose group,with 10 mice in each group.Except the blank group,all the other groups of mice were used to establish AGA models by rubbing testosterone(5 mg/mL)externally.After 2 hours of intervention,the minoxidil group and the high group were respectively coated with 5%minoxidil solution and 200 mg/mL formula solutions.The intervention was continued for 16 days.Western blotting(WB)analysis was employed to detect the expression of proteins transforming growth factor-beta 1(TGF-β1),phosphorylated Smad2(p-Smad2),Smad2,phosphorylated Smad3(p-Smad3),and Smad3 in the skin tissue of the modeled area.Results 1118 AGA disease targets and 299 drug targets were identified,185 shared tar

关 键 词：雄激素性脱发 侧柏双参方 网络药理学 转化生长因子-β信号通路 

分 类 号：R285[医药卫生—中药学]