药典中糖尿病相关中成药的组方规律及作用机制分析

Analysis of the Formula Pattern and Mechanism of Action of Diabetes-related Chinese Patent Medicines in the Pharmacopoeia

目的 筛选中医药临床治疗糖尿病和其他相关疾病的应用规律,并从理论上探讨其可能发生的影响和机制。方法 以中国药典及相关国家标准为基础资料来源,运用Excel 2019、SPSS Modeler 18.0、SPSS Statistics 21.0软件,对已经被纳入该标准的中药进行频数统计、关联规则分析、因子分析和聚类分析,再依托BATMAN-TCM系统针对高频药物进行KEGG通路分析,构建药物-靶点-通路-疾病之间的关联图谱。结果 在药典及相关国家标准中,有70个临床治疗糖尿病及相关疾病的中成药处方被纳入研究,共151味中药,其中使用频数≥10的药物17种,前三位分别是黄芪、天花粉和地黄;关联规则分析挖掘了高频药物的潜在主体药对组合,得到核心药对5个;因子分析提取得到6个公因子;聚类分析将其归为3大类;KEGG通路分析得到高频药对黄芪-天花粉,与糖尿病最为相关的疾病有4种,干预糖尿病及其并发症的潜在靶点共9个,相关信号通路共73条。结论 糖尿病的治疗多以益气养阴药为主,临床随症配伍清热药、收涩药、活血药等。高频药对黄芪-天花粉对糖尿病、糖尿病肾病、糖尿病血脂异常、糖尿病神经病变通过多靶点、多通路发挥作用,其机制可能与调控淀粉和蔗糖代谢、胰岛素信号传导途径、组氨酸代谢、神经活性配体与受体的相互作用等有关。

Objective To analyze and summarize the formula pattern of Chinese medicines in the treatment of diabetes and related diseases, and to explore the possible mechanisms of action.Methods With Chinese Pharmacopoeia and related national standards as data sources, frequency statistics, association rule analysis, factor analysis and cluster analysis were performed on the Chinese medicines included in the standards using Excel 2019,SPSS Modeler 18.0 and SPSS Statistics 21.0.Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine(BATMAN-TCM)was employed to conduct Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the high-frequency drugs and drug-target-pathway-disease maps were constructed.Results In the Pharmacopoeia and related national standards, 70 Chinese patent medicine prescriptions for clinical treatment of diabetes and related diseases were included in this study, with a total of 151 Chinese medicines, among which 17 were used with a frequency of ≥10,and the top three Chinese medicines were Radix Astragali seu Hedysari, Radix Trichosanthis and RadixRehmanniae.Association rule analysis mined the potential drug pair combinations of high-frequency drugs, and 5 core drug pairs were obtained.Infactor analysis, 6 common factors were extracted, and they were grouped into 3 main categories by cluster analysis.The KEGG pathway analysis showed that there were 4 diseases most associated with diabetes, 9 potential targets for diabetes and its complications, and 73 related signaling pathways concerning the high-frequency drug pair Radix Astragali seu Hedysari-Radix Trichosanthis.Conclusion Diabetes is mainly treated with Chinese medicines for replenishing qi and nourishing yin, which areclinically combined with heat-clearing, astringent, and blood-activating medicines based on syndrome differentiation.The high-frequency drug pair Astragalus membranaceus-Radix trichosanthis acts on diabetes, diabetic nephropathy, diabetic dyslipidemia, and diabetic neuropathy through multiple targets and pathways, and the mechanism may be related to the regulation of starch and sucrose metabolism, insulin signaling pathway, histidine metabolism, and neuroactive ligand-receptor interaction.