[关键词]
[摘要]
目的 基于数据挖掘和网络药理学技术研究中医药治疗酒精性肝病(ALD)的组方用药规律及潜在作用机 制。方法 检索中国知网、万方数据库、中国生物医学文献数据库和维普中文期刊收录的中医药治疗 ALD 的 相关方剂,根据筛选条件整理后,使用 IBM SPSS Statistics 27.0、IBM SPSS Modeler 18 软件对纳入方剂的中药 进行组方规律、关联规则分析,归纳中药治疗 ALD 的用药规律,获得核心药物组合。以网络药理学技术,筛 选中医药干预 ALD 核心药物组合的活性成分及其作用靶点;用基因本体(GO)和京都基因与基因组百科全书 (KEGG)对主要作用靶点进行富集分析,并以分子对接技术加以验证。结果 共纳入治疗 ALD 的方剂 143 首, 涉及中药 222 味,使用频次≥25 次的高频中药 28 味,关联规则分析得到 8 个核心药物组合。其中“茯苓-白 术-茵陈”与 ALD 交集靶点 215 个,包括蛋白激酶 B(AKT1)、肿瘤坏死因子(TNF)、血管内皮生长因子 A (VEGFA)、白细胞介素 1β(IL-1β)、非受体酪氨酸激酶(SRC)、表皮生长因子受体(EGFR)等 6 个核心靶点, 涉及信号通路 168 条,主要包括癌症通路、磷脂酰肌醇 3-激酶/蛋白激酶 B(PI3K/AKT)信号通路、化学致癌- 活性氧及脂质-动脉粥样硬化等。分子对接结果显示啤酒甾醇、芫花素、去甲氧基茵陈色原酮等主要活性成分 与 AKT1 结合能力较好。结论 核心药组“茯苓-白术-茵陈”的主要活性成分可通过作用于 AKT1、TNF、 VEGFA 等关键靶点蛋白,参与 PI3K/AKT 等关键信号通路的调控,进而发挥抑制炎症反应及细胞凋亡、减缓 肝纤维化、促进肝细胞修复的作用,可为中医药治疗 ALD 研究提供数据支撑与理论指导。
[Key word]
[Abstract]
Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine (TCM) in the treatment of alcoholic liver disease (ALD) based on the technology of data mining and network pharmacology. Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases. After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules. Then,the medication rules of TCM in the treatment of ALD were summarized, and the core drug combinations were obtained. Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology. GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets. Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 highfrequency Chinese medicine were used with a frequency ≥ 25 times. Eight core drug combinations were obtained by associations rule analysis. It has been found that there are 215 intersection targets between “Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae” and ALD, including six core targets of AKT1, TNF, VEGFA,IL-1β,SRC,EGFR. One hundred and sixty-eight of signaling pathways are involved,including cancer pathways, PI3K/AKT signaling pathways, chemical carcinogenesis-reactive oxygen species, lipid and atherosclerosis, etc. Molecular docking results showed that the main active components including cerevisterol, genkwanin and demethoxycapillarisin had good binding ability to AKT1. Conclusion The main active ingredients in “Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae” can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins (AKT1,TNF,and VEGFA) . Subsequently, they play a role in inhibiting inflammatory response and apoptosis, slowing down liver fibrosis, and promoting hepatocyte repair. This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.
[中图分类号]
R285.6;R285.5
[基金项目]
国家自然科学基金面上项目(82174267);河南省中医药科学研究专项课题-重大专项(2023ZYZD15);河南省高校科技创新人才支持计 划项目(22HASTIT048);河南省大学生创新创业训练计划支持项目(202310471029);河南中医药大学第一附属医院大学生创新学习项目(DCXB- 202310)