Chen Xueqin, Yu Jingyue, Lei Huan, Li Lei, Liu Xupin, Liu Bo, Xie Yanfei, Fang Haihong
School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, China.
NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Institute for Drug Control, Nanchang, China.
Curr Comput Aided Drug Des. 2023;19(6):451-464. doi: 10.2174/1573409919666230203144207.
Buyang Huanwu Decoction (BHD) is used to regulate blood circulation and clear collaterals and is widely used in coronary heart disease. However, the active compounds and the mechanism of BHD used to treat restenosis are less understood.
The study aimed to explore the potential mechanism of Buyang Huanwu decoction BHD for the treatment of restenosis using network pharmacology and molecular docking experiments.
The bioactive components of BHD and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopaedia of Traditional Chinese Medicine (ETCM) databases as well as literature. Restenosisassociated therapeutic genes were identified from the OMIM, Drugbank, GEO, and Dis- GeNET databases. Genes related to the vascular smooth muscle cell (VSMC) phenotype were obtained from the gene ontology (GO) database and literature. The core target genes for the drug-disease-VSMC phenotype were identified using the Venn tool and Cytoscape software. Moreover, the "drug-component-target-pathway" network was constructed and analyzed, and pathway enrichment analysis was performed. The connection between the main active components and core targets was analyzed using the AutoDock tool, and PyMOL was used to visualize the results.
The "compound-target-disease" network included 80 active ingredients and 599 overlapping targets. Among the bioactive components, quercetin, ligustrazine, ligustilide, hydroxysafflor yellow A, and dihydrocapsaicin had high degree values, and the core targets included TP53, MYC, APP, UBC, JUN, EP300, TGFB1, UBB, SP1, MAPK1, SMAD2, CTNNB1, FOXO3, PIN1, EGR1, TCF4, FOS, SMAD3, and CREBBP. A total of 365 items were obtained from the GO functional enrichment analysis (p < 0.05), whereas the enrichment analysis of the KEGG pathway identified 30 signaling pathways (p < 0.05), which involved the TGF-β signaling pathway, Wnt signaling pathway, TRAF6-mediated induction of NF-κB and MAPK pathway, TLR7/8 cascade, and others. The molecular docking results revealed quercetin, luteolin, and ligustilide to have good affinity with the core targets MYC and TP53.
The active ingredients in BHD might act on TP53, MYC, APP, UBC, JUN, and other targets through its active components (such as quercetin, ligustrazine, ligustilide, hydroxysafflor yellow A, and dihydrocapsaicin). This action of BHD may be transmitted via the involvement of multiple signaling pathways, including the TGF-β signaling pathway, Wnt signaling pathway, TRAF6-mediated induction of NF-κB and MAPK pathway, and TLR7/8 cascade, to treat restenosis by inhibiting the phenotype switching and proliferation of VSMC.
补阳还五汤用于活血化瘀、通络，广泛应用于冠心病治疗。然而，补阳还五汤治疗再狭窄的活性成分及作用机制尚不清楚。
采用网络药理学和分子对接实验，探讨补阳还五汤治疗再狭窄的潜在机制。
从中药系统药理学数据库（TCMSP）、《中药大辞典》以及文献中检索补阳还五汤的生物活性成分及其相应靶点。从人类孟德尔遗传数据库（OMIM）、药物银行数据库（Drugbank）、基因表达综合数据库（GEO）和疾病基因数据库（DisGeNET）中鉴定再狭窄相关治疗基因。从基因本体论（GO）数据库和文献中获取与血管平滑肌细胞（VSMC）表型相关的基因。使用维恩工具和Cytoscape软件确定药物-疾病-VSMC表型的核心靶基因。此外，构建并分析“药物-成分-靶点-通路”网络，并进行通路富集分析。使用AutoDock工具分析主要活性成分与核心靶点之间的联系，并使用PyMOL软件可视化结果。
“化合物-靶点-疾病”网络包含80种活性成分和599个重叠靶点。在生物活性成分中，槲皮素、川芎嗪、藁本内酯、羟基红花黄色素A和二氢辣椒素的度值较高，核心靶点包括TP53、MYC基因、APP、泛素羧基末端水解酶L1、JUN、E1A结合蛋白P300、转化生长因子β1（TGFB1）、泛素B、特异性蛋白1（SP1）、丝裂原活化蛋白激酶1（MAPK1）、SMAD2、β-连环蛋白（CTNNB1）、叉头框蛋白O3（FOXO3）、肽基脯氨酰顺反异构酶NIMA相互作用蛋白1（PIN1）、早期生长反应蛋白1（EGR1）、转录因子4（TCF4）、FOS、SMAD3和环磷腺苷效应元件结合蛋白（CREBBP）。GO功能富集分析共获得365项（p<0.05），KEGG通路富集分析确定了30条信号通路（p<0.05）, 包括TGF-β信号通路、Wnt信号通路、肿瘤坏死因子受体相关因子6（TRAF6）介导的核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路、Toll样受体7/8（TLR7/8）级联反应等。分子对接结果显示，槲皮素、木犀草素和藁本内酯与核心靶点MYC和TP53具有良好的亲和力。
补阳还五汤中的活性成分可能通过其活性成分（如槲皮素、川芎嗪、藁本内酯、羟基红花黄色素A和二氢辣椒素）作用于TP53、MYC、APP、泛素羧基末端水解酶L1、JUN等靶点。补阳还五汤的这一作用可能通过多种信号通路介导，包括TGF-β信号通路、Wnt信号通路、TRAF6介导的NF-κB和MAPK信号通路、TLR7/8级联反应等，通过抑制VSMC表型转换和增殖来治疗再狭窄。
