目的 基于網(wǎng)絡(luò)藥理學(xué)、分子對(duì)接技術(shù)探究姜黃素治療代謝相關(guān)性脂肪性肝病潛在靶點(diǎn)，并探討其作用機(jī)制。方法 通過SwissTargetPrediction、TargetNet數(shù)據(jù)庫(kù)篩選出姜黃素的潛在作用靶點(diǎn)；檢索GeneCards、OMIM、DisGeNET數(shù)據(jù)庫(kù)獲取代謝相關(guān)性脂肪性肝病的靶點(diǎn)信息；利用Venny 2.1獲取姜黃素與代謝相關(guān)性脂肪性肝病的交集靶點(diǎn)；采用STRING數(shù)據(jù)庫(kù)構(gòu)建交集靶點(diǎn)的蛋白相互作用（PPI）網(wǎng)絡(luò)圖并使用Cytoscape 3.7.0軟件進(jìn)行網(wǎng)絡(luò)拓?fù)浞治龊Y選關(guān)鍵靶點(diǎn)；基于DAVID平臺(tái)對(duì)交集靶點(diǎn)進(jìn)行基因本體論（GO）和京都基因與基因組百科全書（KEGG）富集分析，進(jìn)一步通過Cytoscape建立“藥物–靶點(diǎn)–通路”網(wǎng)絡(luò)探究姜黃素治療代謝相關(guān)性脂肪性肝病的潛在作用機(jī)制；選取節(jié)degree值排名前10位的核心靶點(diǎn)，使用Ledock軟件對(duì)配體和受體進(jìn)行分子對(duì)接，并將結(jié)果可視化。結(jié)果 預(yù)測(cè)得到姜黃素靶點(diǎn)200個(gè)，篩選、去重得到疾病靶點(diǎn)2 092個(gè)，最后得到交集靶點(diǎn)63個(gè)。排名前5位的關(guān)鍵靶點(diǎn)分別為腫瘤壞死因子（TNF）、蛋白激酶B1（Akt1）、信號(hào)轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活劑3（STAT3）、前列腺素G/H合酶2（PTGS2）、雌激素受體（ESR1）。GO和KEGG富集分析主要指向癌癥中的通路、脂質(zhì)與動(dòng)脈粥樣硬化、糖尿病并發(fā)癥中的晚期糖基化終產(chǎn)物受體（AGE-RAGE）信號(hào)通路、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信號(hào)通路等，分子對(duì)接結(jié)果顯示姜黃素與關(guān)鍵靶點(diǎn)對(duì)接結(jié)合能均小于-5 kcal/mol。結(jié)論 姜黃素可能通過TNF、Akt1、STAT3、PTGS2、ESR1、細(xì)胞凋亡調(diào)節(jié)因子（Bcl-2）等多個(gè)靶點(diǎn)，調(diào)節(jié)AGE-RAGE信號(hào)通路、脂質(zhì)與動(dòng)脈粥樣硬化、糖尿病并發(fā)癥中的AGE-RAGE信號(hào)通路等多條信號(hào)通路，通過抗炎、抗氧化、調(diào)節(jié)糖脂代謝等來發(fā)揮治療代謝相關(guān)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

潛江市公益性行業(yè)科研計(jì)劃項(xiàng)目（2023GYX001）