[关键词]
[摘要]
目的 从中药剂量和成分含量因素分析大黄、枳实和厚朴因配比不同而疗效作用机制产生差异的原因。方法 通过公共数据平台收集大黄、枳实、厚朴的中药剂量、关键化学成分及其含量,以及各成分作用的靶点。通过网络药理学和蛋白质相互作用(protein-protein interaction,PPI)网络分析确定厚朴三物汤治疗胃炎、小承气汤治疗肠梗阻、厚朴大黄汤治疗炎症性肠病的关键靶点。引入中药剂量和成分含量,从“中药-成分-靶点”计算靶点受控力,分析剂量和成分含量对靶点排序的影响,确定受控前后的核心靶点,进行基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,筛选出排名前5的靶点,并与关键成分进行分子对接。结果 共得到18个关键化学成分、246个药物靶点,与胃炎、肠梗阻、炎症性肠病的疾病靶点取交集分别有217、200、219个靶点。靶点受控力结果发现,前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)、雌激素受体1(estrogen receptor 1,ESR1)、过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor gamma,PPARG)、细胞周期蛋白A2(cyclin A2,CCNA2)等靶点基因受控前后排序变化明显,可能是潜在的关键基因,并通过癌症中的蛋白聚糖、白细胞介素-17、肿瘤坏死因子、内分泌抵抗信号通路等途径参与肠道运动、胃黏膜屏障功能、炎症反应等病理改变。分子对接结果表明PTGS2与芦荟大黄素具有最低结合能(−5.68 kcal/mol),结合稳定。结论 考虑中药剂量和成分含量因素后,从“中药-成分-靶点”分析大黄、枳实和厚朴因配比不同对靶点影响的差异,为探究中药复方的量效关系提供了新的途径。
[Key word]
[Abstract]
Objective To analyze the reasons for the differences in the mechanism of action of Dahuang (Rhei Radix et Rhizoma), Zhishi (Aurantii Fructus Immaturus) and Houpo (Magnoliae Officinalis Cortex) due to different dose ratios from the factors of traditional Chinese medicine(TCM) dose and component content. Methods Through the public data platform, the TCM dosage, key chemical components and content determination of Rhei Radix et Rhizoma, Aurantii Fructus Immaturus and Magnoliae Officinalis Cortex were collected, as well as the targets of each component. Identifying the key targets of Houpo Sanwu Decoction for treating gastritis, Xiao Chengqi Decoction for treating intestinal obstruction, and Houpu Dahuang Decoction for treating inflammatory bowel disease through network pharmacology and protein-protein interaction (PPI) network analysis. The dose and component content of TCM were added, and the target-controlled force was calculated from “Chinese medicine-component-target”. The effect of dose and component content on target sequencing was analyzed, and gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the core targets before and after control. The top five targets were screened and molecular docking was performed with the key components. Results A total of 18 key components and 246 drug targets were obtained, which intersected with disease targets for gastritis, intestinal obstruction, and inflammatory bowel disease, yielding 217, 200, and 219 targets, respectively. Observing the results of target control force, it was found that target genes such as prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), peroxisome proliferator activated receptor gamma (PPARG) and cyclin A2 (CCNA2) showed significant changes in ranking before and after control, which may be potential key genes. They are involved in pathological changes such as intestinal motility, gastric mucosal barrier function, and inflammatory responses through proteoglycans in cancer, interleukin-17 (IL-17), tumor necrosis factor (TNF), and endocrine resistance signaling pathways and other pathways. Molecular docking results showed that PTGS2 had the lowest binding energy (−5.68 kcal/mol) with aloe emodin, and the binding was stable. Conclusion After considering the dosage and component content of TCM, the analysis of the differences in the impact of targets due to different ratios of Rhei Radix et Rhizoma, Aurantii Fructus Immaturus and Magnoliae Officinalis Cortex from the “TCM-component-target” perspective provides a new approach to explore the dose-effect relationship of TCM formulas.
[中图分类号]
R285
[基金项目]
国家自然科学基金面上项目(82274215);国家自然科学基金面上项目(82474352);湖南省中医药管理局重点项目(A2024011,2023-24);湖南省自然科学基金项目(2023JJ60124);湖南省重点研发计划(2022SK2014);湖南省教育厅科学研究重点项目(22A0255,22A0281);长沙市自然科学基金项目(kq2202265);湖南中医药大学研究生创新项目(2023CX137)