Liu Tianfu, Liu Jianbo, Hao Liang
China Medical University-The Queen's University of Belfast Joint Collage, China Medical University, Shenyang 110122, Liaoning Province, China.
Shanxi Three-Principles & Six-Disease Institute of Traditional Chinese Medicine, Taiyuan 030001, Shanxi Province, China.
Evid Based Complement Alternat Med. 2021 Jul 27;2021:9925556. doi: 10.1155/2021/9925556. eCollection 2021.
Coronary heart disease (CHD) is one of the most important complications of diabetes mellitus, having a high disability fatality rate. Qiweitangping is a Chinese medicine to control diabetes (type 1 and type 2 diabetes) and complications, having been used in clinic for more than 20 years, with the expected therapeutic effect. In a previous clinical study, the total effective rate of the drug for the treatment of type 2 diabetes reached 92.7%. However, the mechanism of the treatment process is unclear. Therefore, this research was conducted to explore the mechanism of treating diabetic coronary heart disease with the assistance of bioinformatics methods.
The TCMSP database was used to collect the effective chemical constituents of Qiweitangping and the target genes of the chemical constituents, and the related genes of diabetic CHD were obtained from the GeneCard database. Furthermore, the intersection was found between the target gene of the drug and the related gene of the disease to obtain the candidate genes; the STRING database and DAVID database were used to perform protein interaction analysis and KEGG enrichment analysis on the candidate genes. Also, molecular docking was used for auxiliary verification. Finally, a "drug component-gene target-pathway" network was constructed by using Cytoscape software.
Sixty-two effective chemical components including naringin, diosgenin, formogenin, isorolin, and isocryptanshinone, fifty-nine candidate target genes (such as AKT1, CASP3, and VEGF-A), and thirty-nine related pathways in Qiweitangping were obtained. In addition, two pairs (CASP-naringenin and STAT3-cryptotanshinone) of molecular docking results showed good affinity (<-5.00 kcal/mol).
The results of the study indicate that Qiweitangping treats diabetic CHD with multiple chemical components. Its mechanism of action may be related to the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and ErbB signaling pathway. STAT3 and CASP genes have been verified by molecular docking to have a relatively good combination with Qiweitangping. This study is the theoretical basis for further experimental study on the treatment mechanism of diabetic CHD with Qiweitangping.
冠心病（CHD）是糖尿病最重要的并发症之一，致残致死率高。芪味糖平是一种用于控制糖尿病（1型和2型糖尿病）及其并发症的中药，已在临床应用20多年，具有预期的治疗效果。在之前的一项临床研究中，该药物治疗2型糖尿病的总有效率达到92.7%。然而，其治疗过程的机制尚不清楚。因此，本研究借助生物信息学方法探索芪味糖平治疗糖尿病性冠心病的机制。
利用中药系统药理学数据库与分析平台（TCMSP）数据库收集芪味糖平的有效化学成分及其化学成分的靶基因，并从基因卡片（GeneCard）数据库中获取糖尿病性冠心病的相关基因。此外，找出药物的靶基因与疾病的相关基因之间的交集以获得候选基因；利用STRING数据库和DAVID数据库对候选基因进行蛋白质相互作用分析和KEGG富集分析。同时，采用分子对接进行辅助验证。最后，使用Cytoscape软件构建“药物成分-基因靶点-通路”网络。
获得了包括柚皮苷、薯蓣皂苷元、知母皂苷元、异鼠李素和异隐丹参酮在内的62种有效化学成分、59个候选靶基因（如AKT1、CASP3和VEGF - A）以及芪味糖平中的39条相关通路。此外，两对（CASP - 柚皮苷和STAT3 - 隐丹参酮）分子对接结果显示出良好的亲和力（<-5.00 kcal/mol）。
研究结果表明，芪味糖平通过多种化学成分治疗糖尿病性冠心病。其作用机制可能与缺氧诱导因子-1（HIF - 1）信号通路、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K - Akt）信号通路和表皮生长因子受体（ErbB）信号通路有关。通过分子对接验证，STAT3和CASP基因与芪味糖平具有较好的结合。本研究为进一步开展芪味糖平治疗糖尿病性冠心病作用机制的实验研究提供了理论依据。
