[关键词]
[摘要]
目的 通过网络药理学方法探讨黄连解毒汤治疗动脉粥样硬化(AS)的潜在分子生物学机制。方法 从中药系统药理学分析平台(TCMSP)及文献资料中寻找与黄连解毒汤中4味中药相关的所有成分和作用靶点,并构建药物分子-靶点网络;通过TTD、DrugBank、DisGeNET数据库筛选与AS相关的靶标,利用STRING平台构建药物-疾病靶点交互网络;对核心靶点进行网络拓扑分析,利用DAVID数据库对核心靶点蛋白进行GO生物过程分析及KEGG通路富集分析,并构建黄连解毒汤活性成分-AS靶点-KEGG通路多维网络关系图。结果 根据筛选条件[口服生物利用度(OB)≥30%、类药性(DL)≥0.18)]及查阅文献资料共得到71个活性成分,165个药物潜在靶点。黄连解毒汤中活性成分主要有谷甾醇、槲皮素、小檗碱、去氢丹参酮IIA、黄芩新素等能够干预AS形成。3个疾病数据库以“atherosclerosis”为搜索条件共收集到175个疾病靶点。根据度(degree)值筛选出黄连解毒汤干预AS的核心靶标蛋白223个,主要涉及NOS2、NOS3、PTGS2、TNF、CYP2C9、HMOX1等。GO生物过程分析根据错误发现率(FDR)≤0.05,确定50个条目,主要包括SRP依赖的靶向膜转运蛋白、核转录的mRNA分解代谢过程、病毒转录、核糖体核糖核酸处理、翻译等生物分析过程。KEGG富集结果显示有74条通路与AS相关,主要涉及到核糖体通路、病毒致癌通路、参与细胞周期通路、雌激素信号通路通路等。结论 黄连解毒汤治疗AS是多成分、多靶点、多途径相互作用的结果,为黄连解毒汤的临床应用以及AS相关疾病的基础或临床研究提供一定的理论依据,同时对新药的研发与应用具有一定的参考价值。
[Key word]
[Abstract]
Objective To explore the potential molecular mechanism of Huanglian Jiedu Decoction in the treatment of atherosclerosis (AS) through pharmacology network. Methods By identifying all the composition and effect targets of four herbal ingredients in Huanglian Jiedu Decoction from TCMSP platforms and literatures, and the pharmaceutical molecular-target network was constructed. The interaction network of drug-disease target by STRING platform was constructed by screening AS related targets through TTD, DrugBank and DisGeNET databases. The centre targets were analyzed by network topology. DAVID database was used to perform GO biological process analysis and KEGG pathway enrichment analysis of centre target proteins, and further construct a multi-dimensional network relationship diagram of the active component-AS target-KEGG pathway of Huanglian Jiedu Decoction. Results A total of 71 active ingredients and 165 potential drug targets were obtained according to the screening conditions (OB ≥ 30%, DL ≥ 0.18) and accessing literatures. The main active ingredients in Huanglian Jiedu Decoction included sitosterol, quercetin, berberine, dehydrotanshinone IIA and neobaicalein, which could interfere with the formation of AS. A total of 175 disease targets were collected from the three disease databases under the search criteria of "atherosclerosis". According to Degree, 223 centre target proteins of Huanglian Jiedu Decoction were screened, mainly invovling NOS2, NOS3, PTGS2, TNF, CYP2C9 and HMOX1, et al. GO biological process analysis identified 50 entries based on false discovery rate (FDR) ≤ 0.05, mainly including SRP-dependent targeting membrane transporters, nuclear-transcribed mRNA catabolic process, viral transcription, rRNA processing, translation and other bioanalysis process. The result of KEGG enrichment analysis showed 74 pathways were associated with AS, mainly involved in ribosome pathway, viral carcinogenesis pathway, cell cycle pathway, estrogen signaling pathway, et al. Conclusion Huanglian Jiedu Decoction can treat AS through multi-ingredient, multi-target and multi-pathway interaction, which provides a theoretical basis for the clinical application of Huanglian Jiedu Decoction and the basic or clinical research of AS-related diseases. Meanwhile, it has a certain reference value for the research and development of new drugs and its application.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金面上项目(81874372);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(zyzx1501);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(zyzx1902)