Zhou Kewei, Chen Chang, Cai Hexin, Lian Zuqian, Wang Luping, Li Qinghuo, Wang Cancan, Wu Xiaoqian, Wang Panxia
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2025 Aug 4;16:1628625. doi: 10.3389/fphar.2025.1628625. eCollection 2025.
BACKGROUND: Hypertrophic cardiomyopathy is an independent risk factor for heart failure. () is a traditional Chinese medicine with a variety of chemical components and pharmacological effects. The mechanisms of for treating hypertrophic cardiomyopathy are still unclear. METHODS: In this study, we used network pharmacology techniques combined with bioinformatics analysis and identified the active ingredient in to protect against hypertrophic cardiomyopathy. We analyzed the Gene Expression Omnibus (GEO) database from human heart tissue with hypertrophic cardiomyopathy to reveal the potential targets. Finally, molecular docking and validation were used to reveal the binding of the potential targets and the main active component of . RESULTS: Our results revealed that there are five main active ingredients of (nobiletin, naringenin, sitosterol, 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl) chroman-4-one, and citromitin). By analyzing the intersecting genes between and hypertrophic cardiomyopathy, 40 hub genes were obtained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the responses to oxidative stress and fatty acids were the main pathways for to act against hypertrophic cardiomyopathy. The protein-protein interaction analysis results showed that the main active ingredients of were nobiletin and naringenin, while peroxisome proliferator-activated receptors (PPAR)α might be the potential targets of in treating hypertrophic cardiomyopathy. The molecular docking results showed that the main active ingredient, nobiletin, could bind to PPARα with a strong hydrogen-bonding interaction force. results validated that nobiletin might directly bind to PPARα, thereby increasing the expression of lipid metabolism-related genes and relieving hypertrophic responses of cardiomyocytes. CONCLUSION: The nuclear receptor PPARα might be the potential endogenous receptor of the active ingredients of .
背景:肥厚型心肌病是心力衰竭的独立危险因素。(此处原文括号处内容缺失,未完整给出具体所指中药名称)是一种具有多种化学成分和药理作用的中药。其治疗肥厚型心肌病的机制尚不清楚。 方法:在本研究中,我们运用网络药理学技术结合生物信息学分析,确定了(此处原文括号处内容缺失,未完整给出具体所指中药名称)中预防肥厚型心肌病的活性成分。我们分析了来自肥厚型心肌病患者心脏组织的基因表达综合数据库(GEO)以揭示潜在靶点。最后,利用分子对接和(此处原文缺失具体验证方式)验证来揭示潜在靶点与(此处原文括号处内容缺失,未完整给出具体所指中药名称)主要活性成分的结合情况。 结果:我们的结果显示(此处原文括号处内容缺失,未完整给出具体所指中药名称)有五种主要活性成分(川陈皮素、柚皮素、甾醇、5,7 - 二羟基 - 2 - (3 - 羟基 - 4 - 甲氧基苯基)苯并二氢吡喃 - 4 - 酮和枸橼素)。通过分析(此处原文括号处内容缺失,未完整给出具体所指中药名称)与肥厚型心肌病之间的交集基因,获得了40个枢纽基因。基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析表明,对氧化应激和脂肪酸的反应是(此处原文括号处内容缺失,未完整给出具体所指中药名称)对抗肥厚型心肌病的主要途径。蛋白质 - 蛋白质相互作用分析结果显示,(此处原文括号处内容缺失,未完整给出具体所指中药名称)的主要活性成分是川陈皮素和柚皮素,而过氧化物酶体增殖物激活受体(PPAR)α可能是(此处原文括号处内容缺失,未完整给出具体所指中药名称)治疗肥厚型心肌病的潜在靶点。分子对接结果表明,主要活性成分川陈皮素能以较强的氢键相互作用力与PPARα结合。(此处原文缺失具体验证方式)结果证实川陈皮素可能直接与PPARα结合,从而增加脂质代谢相关基因的表达并减轻心肌细胞的肥厚反应。 结论:核受体PPARα可能是(此处原文括号处内容缺失,未完整给出具体所指中药名称)活性成分的潜在内源性受体。
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