Gao Siqi, Gao Tingting, Li Lizheng, Wang Shule, Hu Jie, Zhang Ruijing, Zhou Yun, Dong Honglin
Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Genes Nutr. 2024 Jul 23;19(1):13. doi: 10.1186/s12263-024-00748-3.
Employing network pharmacology and molecular docking, the study predicts the active compounds in garlic and elucidates their mechanism in inhibiting the development of alcoholic liver disease (ALD). ALD is a global chronic liver disease with potential for hepatocellular carcinoma progression.
The main active ingredients and targets of garlic were identified through screening the TCMSP, TCM-ID, and ETCM databases. ALD disease targets were sourced from DisGeNET, GeneCards, and DiGSeE databases, and intervention targets for garlic were determined through intersections. Protein interaction networks were constructed using the STRING platform, and GO and KEGG pathway enrichment analyses were performed with R software. The garlic component-disease-target network was established using Cytoscape software. Validation of active ingredients against core targets was conducted through molecular docking simulations using AutoDock Vina software. Expression validation of core targets was carried out using human sequencing data of ALD obtained from the GEO database.
Integration of garlic drug targets with ALD disease targets identified 83 target genes. Validation through an alcohol-induced ALD mouse model supported certain network pharmacology findings, suggesting that garlic may impede disease progression by mitigating the inflammatory response and promoting ethanol metabolism.
This study provides insights into the potential therapeutic mechanisms of garlic in inhibiting ALD development. The identified active ingredients offer promising avenues for further investigation and development of treatments for ALD, emphasizing the importance of botanical remedies in liver disease management.
本研究运用网络药理学和分子对接技术，预测大蒜中的活性成分，并阐明其抑制酒精性肝病（ALD）发展的机制。ALD是一种全球性的慢性肝病，有发展为肝细胞癌的潜在风险。
通过筛选中药系统药理学数据库（TCMSP）、中医综合数据库（TCM-ID）和中药成分靶点数据库（ETCM），确定大蒜的主要活性成分和靶点。ALD疾病靶点来源于疾病基因数据库（DisGeNET）、基因卡片数据库（GeneCards）和疾病基因搜索引擎数据库（DiGSeE），通过交集确定大蒜的干预靶点。使用STRING平台构建蛋白质相互作用网络，并使用R软件进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。使用Cytoscape软件建立大蒜成分-疾病-靶点网络。通过使用AutoDock Vina软件进行分子对接模拟，对活性成分针对核心靶点进行验证。使用从基因表达综合数据库（GEO）获得的ALD人类测序数据对核心靶点进行表达验证。
将大蒜药物靶点与ALD疾病靶点整合，确定了83个靶基因。通过酒精诱导的ALD小鼠模型进行验证，支持了某些网络药理学研究结果，表明大蒜可能通过减轻炎症反应和促进乙醇代谢来阻碍疾病进展。
本研究为大蒜抑制ALD发展的潜在治疗机制提供了见解。所确定的活性成分可为ALD治疗的进一步研究和开发提供有前景的途径，强调了植物疗法在肝病管理中的重要性。
