Yang Yang, Yang Kuo, Hao Teng, Zhu Guodong, Ling Ruby, Zhou Xuezhong, Li Ping
The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.
Beijing Key Lab of Traffic Data Analysis and Mining, School of Computer and Information Technology, Beijing Jiaotong University, Beijing, China.
Front Physiol. 2018 May 8;9:489. doi: 10.3389/fphys.2018.00489. eCollection 2018.
Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms). The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein-protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula's CHD modules). The molecular characteristics of LXNX formula's CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms). We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups. G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula's pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that (Banxia) has relatively strong adjustive functions on the two key targets.
采用网络药理学方法研究中药复方连夏宁心方治疗冠心病（CHD）及其疾病表型（CHD相关疾病和症状）的潜在分子机制。从生物医学数据库和已发表的生物医学文献中手动整理出与连夏宁心方药材相关的不同种子基因列表、连夏宁心方缓解的CHD共病疾病和症状（共病疾病和症状）。使用模块富集分析在蛋白质-蛋白质相互作用（PPI）网络中识别与连夏宁心方靶点相关的CHD相关疾病模块（连夏宁心方的CHD模块）。通过基因本体和通路方面的功能富集分析研究连夏宁心方CHD模块的分子特征。我们进行最短路径分析以探索连夏宁心方药物靶点与CHD相关疾病表型（如共病疾病和症状）之间的相互作用。我们确定了两个与CHD相关的重要疾病模块（即M146和M203），它们是连夏宁心方药材的作用靶点。通路和基因本体术语功能分析结果表明，M146的G蛋白偶联受体信号通路和M203的细胞蛋白质代谢过程是各自模块的重要功能通路。连夏宁心方药物靶点与上述疾病模块之间的最短路径分析进一步证实了这一点。此外，促肾上腺皮质激素释放激素（CRH）和利钠肽前体A（NPPA）是仅有的两个与各自的CHD模块以及共病疾病和症状基因组最短路径长度较低（平均短于3）的连夏宁心方靶点蛋白。G蛋白偶联受体信号通路和细胞蛋白质代谢过程是连夏宁心方治疗CHD疾病表型的关键通路，其中CRH和NPPA是连夏宁心方的两个关键药物靶点。来自中草药药理学数据库的进一步证据表明，半夏对这两个关键靶点具有相对较强的调节作用。
