Meng Xiang-Fei, Zhang Feng-Rong, Wang Bo, Tang Shi-Huan
Wangjing Hospital, China Academy of Chinese Medical Sciences Beijing 100102, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700,China.
Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(3):764-775. doi: 10.19540/j.cnki.cjcmm.20211103.701.
The core prescriptions and formulation characteristics in the treatment of edema by traditional Chinese medicine(TCM) masters were analyzed through data mining and their mechanisms were explored by network pharmacology. We collected journal reports on the treatment of edema by TCM masters in three sessions from China National Knowledge Infrastructure(CNKI) and constructed a database by Traditional Chinese Medicine Inheritance Support System 3.0. The prescriptions in the case studies were analyzed by association rules and k-means clustering. The chemical components and targets of Chinese medicines in core prescriptions were collected through TCMSP and TCMID. Edema-related targets were collected from DrugBank and GeneCards. The protein-protein interaction(PPI) network was constructed by STRING and the core targets were screened out. FunRich 3.1.3 was used to enrich the expression sites of core prescriptions. Metascape was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of intersection targets. Cytoscape 3.6.0 was used to visualize the "Chinese medicine-active ingredient-core target-pathway" network. The results showed that 315 pieces of medical records in the treatment of edema by TCM masters were obtained and five core prescriptions were analyzed by association rules and k-means clustering. Core prescription 1 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Glycyrrhizae Radix et Rhizoma, and Codonopsis Radix, involving 166 chemical components and 1 125 targets. Core prescription 2 contained Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Paeoniae Radix Rubra, and Angelicae Sinensis Radix, involving 138 chemical components and 1 112 targets. Core prescription 3 contained Poria, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Alismatis Rhizoma, and Coicis Semen, involving 126 chemical components and 1 121 targets. Core prescription 4 contained Poria, Forsythiae Fructus, Atractylodis Macrocephalae Rhizoma, Imperatae Rhizoma, Cicadae Periostracum, and Coicis Semen, involving 58 chemical components and 820 targets. Core prescription 5 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Trionycis Carapax, and Dioscoreae Rhizoma, involving 68 chemical components and 919 targets. The core targets of core prescriptions included AKT1, ALB, CASP3, MAPK3, EGFR, SRC, MAPK1, and TNF. The potential targets of core prescriptions in the treatment were highly expressed in the stomach, bladder, lung, and kidney. KEGG pathways were enriched in inflammation and cell cycle pathways, especially the inflammation-relation pathways. The therapeutic effect of core prescriptions on edema is presumedly achieved by tonifying the spleen, draining water, activating blood, and benefiting Qi to resist inflammation and regulate the immune system. This study is expected to provide references for the summary of TCM masters' experience and new drug development.
通过数据挖掘分析中医名家治疗水肿的核心方剂及配伍特点，并运用网络药理学探讨其作用机制。我们从中国知网（CNKI）收集了三届中医名家治疗水肿的期刊报道，并通过中医传承辅助系统3.0构建数据库。采用关联规则和k均值聚类分析案例中的方剂。通过中药系统药理学数据库与分析平台（TCMSP）和中药整合数据库（TCMID）收集核心方剂中中药的化学成分和靶点。从药物数据库（DrugBank）和基因卡片（GeneCards）收集水肿相关靶点。利用STRING构建蛋白质-蛋白质相互作用（PPI）网络并筛选出核心靶点。使用FunRich 3.1.3对核心方剂的表达位点进行富集。运用Metascape对交集靶点进行京都基因与基因组百科全书（KEGG）富集分析。使用Cytoscape 3.6.0可视化“中药-活性成分-核心靶点-通路”网络。结果显示，获得了315篇中医名家治疗水肿的医案，并通过关联规则和k均值聚类分析出5个核心方剂。核心方剂1包含茯苓、白术、黄芪、泽泻、甘草、党参，涉及166种化学成分和1125个靶点。核心方剂2包含黄芪、丹参、茯苓、川芎、赤芍、当归，涉及138种化学成分和1112个靶点。核心方剂3包含茯苓、丹参、黄芪、白术、泽泻、薏苡仁，涉及126种化学成分和1121个靶点。核心方剂4包含茯苓、连翘、白术、白茅根、蝉蜕、薏苡仁，涉及58种化学成分和820个靶点。核心方剂5包含茯苓、白术、黄芪、泽泻、鳖甲、山药，涉及68种化学成分和919个靶点。核心方剂的核心靶点包括蛋白激酶B1（AKT1）、白蛋白（ALB）、半胱天冬酶3（CASP3）、丝裂原活化蛋白激酶3（MAPK3）、表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶（SRC）、丝裂原活化蛋白激酶1（MAPK1）和肿瘤坏死因子（TNF）。核心方剂治疗水肿的潜在靶点在胃、膀胱、肺和肾中高表达。KEGG通路富集于炎症和细胞周期通路，尤其是炎症相关通路。核心方剂治疗水肿的作用可能是通过健脾、利水、活血、益气来抵抗炎症和调节免疫系统实现的。本研究有望为总结中医名家经验和新药研发提供参考。
