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目的 采用网络药理学与分子对接方法探讨姜黄素治疗糖尿病脑病的机制。方法 通过SuperPred、TargetNet、SwissTargetPrediction等数据库鉴定姜黄素干预糖尿病脑病的潜在靶点,利用STRING数据库构建了蛋白相互作用(PPI)网络,并通过Cytoscape 3.7.2软件进行拓扑分析,识别出核心靶点,并利用DAVID数据库进行潜在靶点的基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。对核心靶点和活性成分进行分子对接活性验证。结果 识别出姜黄素治疗糖尿病脑病的144个潜在靶点,得到13个核心靶点,包括蛋白激酶B1(Akt1)、信号转导和转录激活因子3(STAT3)、Src激酶(SRC)、热休克蛋白HSP90-α(HSP90AA1)、表皮生长因子受体(EGFR)、淀粉样前体蛋白(APP)、糖原合酶激酶3β(GSK3B)、雌激素受体α(ESR1)、核因子κB p65(RELA)、E1A结合蛋白p300(EP300)、前列腺素内过氧化物合酶-2(PTGS2)、细胞间黏附分子-1(ICAM1)、肿瘤坏死因子(TNF)。GO分析表明,姜黄素抗糖尿病脑病作用涉及多种生物过程、细胞组分和分子功能,包括对凋亡过程负调控的响应、炎症反应和蛋白激酶活性。KEGG通路分析确定了糖尿病并发症中的晚期糖基化终末产物(AGEs)与其受体(RAGE)信号通路、流体剪切应力与动脉粥样硬化、内分泌抵抗、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B1(Akt)等作用途径。分子对接结果显示,8个核心靶点均与姜黄素有强烈的结合。结论 姜黄素能够穿过血脑屏障,其良好的生物利用度使其成为一种有前途的口服候选药物。
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[Abstract]
Objective To investigate the mechanism of curcumin in treatment of diabetic encephalopathy by using network pharmacology and molecular docking methods. Methods Potential targets of curcumin intervention in diabetic encephalopathy were identified through databases such as SuperPred, TargetNet, and SwissTargetPrediction, a protein interaction network was constructed using the STRING database, and topological analysis was carried out through Cytoscape3.7.2 software to identify core targets. The DAVID database was used for GO and KEGG enrichment analysis of potential targets. The core target and active ingredients were verified for molecular docking activity. Results 144 Potential targets for curcumin treatment of diabetic encephalopathy were identified, and 13 core targets were obtained, including Akt1, STAT3, SRC, HSP90AA1, EGFR, APP, GSK3B, ESR1, RELA, EP300, PTGS2, ICAM1, TNF. GO analysis showed that the anti- diabetic encephalopathy effect of curcumin involves multiple biological processes, cellular components and molecular functions, including responses to negative regulation of the apoptosis process, inflammatory responses and protein kinase activity. KEGG pathway analysis identified the AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, endocrine resistance, and PI3K/Akt signaling pathways. Molecular docking results showed that all eight core targets had strong binding to curcumin. Conclusion Curcumin can cross the blood-brain barrier and its excellent bioavailability makes it a promising candidate for oral medication.
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