基于网络药理学探讨银杏叶提取物对氧化应激的作用

Exploring the Effects of Ginkgo biloba on Oxidative Stress Based on Network Pharmacology

摘要: 目的：心血管病患病率处于持续上升阶段，银杏叶具有多种药用功效，由于银杏叶成分复杂，其抗氧化应激的关键成分及关键靶点仍不明确。在本研究中基于网络药理学探讨银杏叶提取物抗氧化应激的作用机制。方法：通过文献检索与中药系统药理学数据库搜索等综合方法筛选银杏叶中的主要活性成分，借助SwissTargetPrediction预测成分作用靶点；通过GeneCards和OMIM数据库平台获取氧化应激的相关靶点，通过Venny 2.1.0平台获取银杏叶活性成分抗氧化应激作用的靶点，导入STRING平台及Cytoscape 3.9.1软件构建蛋白互作网络与核心靶点网路图，通过DAVID数据库进行GO功能富集分析与KEGG通路富集分析。结果：以口服生物利用度 ≥ 30％和类药性 ≥ 0.18作为条件确定银杏叶的主要活性成分27个，拮抗氧化应激的潜在靶标49个，GO分析结果显示银杏叶拮抗脑缺血的关键靶点主要集中在基因表达的正负调控、miRNA转录的负调控、对外源物质刺激的响应、细胞对活性氧的响应等生物过程以及酶结合、血红素结合、相同蛋白结合、JUN激酶活性、丝裂原活化蛋白激酶(MAPK)活性、蛋白激酶活性等分子功能。KEGG富集分析显示银杏叶可能通过C型凝集素受体(CLRs)信号通路、脂质代谢、活性氧、流体剪切应力和神经营养因子信号通路等信号通路调节发挥其调节清除自由基和调节凋亡等过程。结论：本研究确定了银杏叶在抗氧化应激的活性成分和潜力分子机制，这将为银杏叶进一步开发应用提供依据。

Abstract: Objective: Cardiovascular diseases are on the rise globally, and oxidative stress plays a crucial role in their progression. Ginkgo biloba possesses diverse pharmacological properties, yet the specific active components and molecular targets involved in their antioxidant effects remain unclear. This study aimed to clarify how Ginkgo biloba works as an antioxidant by using a combined method of network pharmacolog. Method: Key active components were identified using literature review and traditional Chinese medicine pharmacology databases, and their targets were predicted via SwissTargetPrediction. Oxidative stress-related targets were retrieved from GeneCards and OMIM, and overlap targets were analyzed using the Venny 2.1.0 platform. We created protein-protein interaction networks using STRING and Cytoscape, and we conducted GO and KEGG enrichment analyses with the DAVID database. Results: A total of 27 active compounds and 49 potential antioxidant targets were identified. GO analysis revealed key roles in gene regulation, reactive oxygen species response, and kinase activities. KEGG pathway enrichment indicates involvement in CLR signals, lipid metabolism, atherosclerosis, and neurotrophic factor signaling. Conclusion: These findings show the important parts and processes that allow Ginkgo biloba to provide antioxidant benefits, giving a basis for its future use in protecting the heart and blood vessels.