基于数据挖掘、网络药理学和分子对接的蒙药方剂治疗肺部感染性疾病的评估
Assessment of pulmonary infectious disease treatment with Mongolian medicine formulae based on data mining, network pharmacology and molecular docking.
作者信息
Zhou Baochang, Qian Zhanhong, Li Qinyu, Gao Yuan, Li Minhui
机构信息
College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010110, China.
Department of Pharmacy, Baotou Medical College, Baotou 014040, China.
出版信息
Chin Herb Med. 2022 Jul 22;14(3):432-448. doi: 10.1016/j.chmed.2022.07.001. eCollection 2022 Jul.
OBJECTIVE
Pulmonary infectious diseases (PID) include viral pneumonia (VP) and pulmonary tuberculosis (PT). Mongolian medicine (MM) is an effective treatment option in China, however, the core group medicines (CGMs) in the treatment of PID and their underlying therapeutic mechanisms remain unclear. In this study, through the method of data mining, the CGMs of MM for the treatment of PID were excavated, and the possible mechanism of action of the CGMs in the treatment of PID was explored by using network pharmacology.
METHODS
First, 89 MM formulae for the treatment of pulmonary infectious diseases collected from , , (Mongolian Medicine Volume), (2007 Edition), and (2014 Edition). The CGMs of MM for PID were excavated through association rule analysis and cluster analysis. Then, the active ingredients and potential targets of the CGMs were obtained from TCMSP, TCMIP, BATMAN-TCM databases. PID targets information was collected from OMIM, GeneCards, and DrugBank databases. The possible targets of CGMs treatment for PID were obtained by intersection. The PPI network was constructed through the STRING database, and the topology analysis of the network was performed. Through the enrichment analysis of the intersection targets by R language, the main action pathways and related target proteins of CGMs in the treatment of PID were screened out. The results were verified by molecular docking.
RESULTS
A total of 89 formulae were included, involving 164 MM herbs. The efficacy of the drugs was mainly cough-suppressing and panting-calming herbs, and heat-clearing herbs. The nature and flavor were mainly bitter and cold. The CGMs of MM to treatment of PID was excavated as the classic famous formula Sanzi Decoction (). A total of 28 candidate components and 237 predicted targets of CGMs were collected, and 61 common targets with PID were obtained, including key compounds such as quercetin, kaempferol, -sitosterol and stigmastero and key targets such as VEGFA, IL6, TP53, AKT1. KEGG enrichment analysis yielded AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways. Molecular docking results showed that the key targets were well matched with the potential active ingredients of CGMs.
CONCLUSION
This study found that MM commonly used cough-suppressing and panting-calming herbs in combination with heat-clearing herbs to treat PID, and the CGMs for the treatment of PID is "". CGMs mainly play a role in the treatment of PID by acting on VEGFA, IL6, TP53, AKT1 and other targets, regulating AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways.
目的
肺部感染性疾病(PID)包括病毒性肺炎(VP)和肺结核(PT)。蒙医药是中国一种有效的治疗选择,然而,蒙医药治疗PID的核心组方及其潜在治疗机制仍不清楚。本研究通过数据挖掘方法,挖掘蒙医药治疗PID的核心组方,并运用网络药理学探讨核心组方治疗PID的可能作用机制。
方法
首先,从《中国医学百科全书·蒙医学》《蒙医方剂学》(2007年版)和《蒙医药学》(2014年版)中收集89首治疗肺部感染性疾病的蒙医方剂。通过关联规则分析和聚类分析挖掘蒙医药治疗PID的核心组方。然后,从中药系统药理学数据库与分析平台(TCMSP)、中药整合药理学平台(TCMIP)、中药系统生物学与药物靶点数据库(BATMAN-TCM)获取核心组方的活性成分和潜在靶点。从在线人类孟德尔遗传数据库(OMIM)、基因卡片数据库(GeneCards)和药物银行数据库(DrugBank)收集PID靶点信息。通过交集得到核心组方治疗PID的可能靶点。通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并对网络进行拓扑分析。运用R语言对交集靶点进行富集分析,筛选出核心组方治疗PID的主要作用通路和相关靶蛋白。通过分子对接验证结果。
结果
共纳入89首方剂,涉及164味蒙药。药物功效主要为止咳平喘类和清热类药材。性味主要为苦、寒。挖掘出蒙医药治疗PID的核心组方为经典名方三子汤。共收集到核心组方的28个候选成分和237个预测靶点,与PID的61个共同靶点,包括槲皮素、山柰酚、β-谷甾醇和豆甾醇等关键化合物以及血管内皮生长因子A(VEGFA)、白细胞介素6(IL6)、肿瘤蛋白p53(TP53)、蛋白激酶B1(AKT1)等关键靶点。京都基因与基因组百科全书(KEGG)富集分析得出晚期糖基化终末产物受体(AGE-RAGE)信号通路、白细胞介素17(IL-17)信号通路和肿瘤坏死因子(TNF)信号通路。分子对接结果显示关键靶点与核心组方潜在活性成分匹配良好。
结论
本研究发现蒙医药常用止咳平喘类药材与清热类药材配伍治疗PID,治疗PID的核心组方为“三子汤”。核心组方主要通过作用于VEGFA、IL6、TP53、AKT1等靶点,调节AGE-RAGE信号通路、IL-17信号通路和TNF信号通路发挥治疗PID的作用。