目的 基于网络药理学、分子对接技术探究姜黄素治疗代谢相关性脂肪性肝病潜在靶点，并探讨其作用机制。方法 通过SwissTargetPrediction、TargetNet数据库筛选出姜黄素的潜在作用靶点；检索GeneCards、OMIM、DisGeNET数据库获取代谢相关性脂肪性肝病的靶点信息；利用Venny 2.1获取姜黄素与代谢相关性脂肪性肝病的交集靶点；采用STRING数据库构建交集靶点的蛋白相互作用（PPI）网络图并使用Cytoscape 3.7.0软件进行网络拓扑分析筛选关键靶点；基于DAVID平台对交集靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，进一步通过Cytoscape建立“药物–靶点–通路”网络探究姜黄素治疗代谢相关性脂肪性肝病的潜在作用机制；选取节degree值排名前10位的核心靶点，使用Ledock软件对配体和受体进行分子对接，并将结果可视化。结果 预测得到姜黄素靶点200个，筛选、去重得到疾病靶点2 092个，最后得到交集靶点63个。排名前5位的关键靶点分别为肿瘤坏死因子（TNF）、蛋白激酶B1（Akt1）、信号转导和转录激活剂3（STAT3）、前列腺素G/H合酶2（PTGS2）、雌激素受体（ESR1）。GO和KEGG富集分析主要指向癌症中的通路、脂质与动脉粥样硬化、糖尿病并发症中的晚期糖基化终产物受体（AGE-RAGE）信号通路、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路等，分子对接结果显示姜黄素与关键靶点对接结合能均小于-5 kcal/mol。结论 姜黄素可能通过TNF、Akt1、STAT3、PTGS2、ESR1、细胞凋亡调节因子（Bcl-2）等多个靶点，调节AGE-RAGE信号通路、脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路等多条信号通路，通过抗炎、抗氧化、调节糖脂代谢等来发挥治疗代谢相关性脂肪性肝病的作用。

Objective To explore the targets of curcumin in treatment of metabolic associated fatty liver disease, and to discuss its mechanisms of action. Methods Targets of curcumin were identified using the SwissTargetPrediction and TargetNet databases, target information for metabolic associated fatty liver disease was retrieved from GeneCards, OMIM, and DisGeNET databases. Venny 2.1 was used to obtain the intersection of curcumin and metabolic associated fatty liver disease targets, STRING database was employed to construct a PPI network for the intersecting targets, and Cytoscape 3.7.0 software was utilized for network topology analysis to identify key targets. DAVID platform was used for GO and KEGG enrichment analysis of the intersecting targets. A “drug–target–pathway” network was established using Cytoscape to investigate the potential mechanisms of curcumin in treating metabolic associated fatty liver disease. Top 10 core targets based on degree value were selected, and molecular docking of the ligand and receptor was performed using Ledock software, with results visualized. Results A total of 200 curcumin targets were predicted, and after filtering and deduplication, 2 092 disease targets were obtained, resulting in 63 intersecting targets. The top five key targets are TNF, Akt1, STAT3, PTGS2, and ESR1, among others. GO and KEGG enrichment analyses mainly pointed to pathways in cancer, lipids and atherosclerosis, AGE-RAGE signaling pathway in diabetes complications, and the PI3K/Akt signaling pathway, etc. Molecular docking results showed that the binding energy of curcumin with key targets was less than -5 kcal/mol. Conclusion Curcumin may act through multiple targets such as TNF, Akt1, STAT3, PTGS2, ESR1, and Bcl-2, to regulate various signaling pathways including the AGE-RAGE signaling pathway, lipids and atherosclerosis, and the AGE-RAGE signaling pathway in diabetes complications, thereby exerting its therapeutic effects on metabolic associated fatty liver disease through anti-inflammatory, antioxidant, and regulation of glucose and lipid metabolism.

R285

潜江市公益性行业科研计划项目（2023GYX001）