School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
School of International Education, Shandong University of Traditional Chinese Medicine, Jinan, China.
Medicine (Baltimore). 2023 May 26;102(21):e33877. doi: 10.1097/MD.0000000000033877.
Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear.
This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations.
The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine-active ingredient-potential target and protein-protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins-ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results.
A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions.
This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD.
银杏叶（GBL）在血管性痴呆（VD）的治疗中起着重要作用，但作用机制尚不清楚。
本研究采用网络药理学、分子对接和分子动力学模拟方法，探讨 GBL 治疗 VD 的作用机制。
采用中药系统药理学数据库、瑞士靶点预测和基因卡片数据库筛选 GBL 的活性成分及相关靶点，采用 OMIM、DrugBank、基因卡片和 DisGeNET 数据库筛选 VD 相关靶点，并用韦恩图识别潜在靶点。使用 Cytoscape 3.8.0 软件和 STRING 平台分别构建中药-活性成分-潜在靶点和蛋白质-蛋白质相互作用网络。使用 DAVID 平台对潜在靶点进行基因本体和京都基因与基因组百科全书通路分析后，采用分子对接分析关键活性成分与靶点的结合亲和力，最后通过分子动力学模拟验证分子对接结果，筛选出结合最好的前 3 个蛋白-配体对。
筛选出 27 种 GBL 活性成分，鉴定出 274 个潜在靶点参与 VD 的治疗。槲皮素、木樨草素、山奈酚和银杏内酯 B 是治疗的核心成分，AKT1、TNF、IL6、VEGFA、IL1B、TP53、CASP3、SRC、EGFR、JUN 和 EGFR 是主要作用靶点。主要生物学过程涉及细胞凋亡、炎症反应、细胞迁移、脂多糖反应、缺氧反应和衰老。PI3K/Akt 似乎是 GBL 治疗 VD 的关键信号通路。分子对接显示活性成分与靶点之间具有较强的结合亲和力。分子动力学模拟结果进一步验证了它们相互作用的稳定性。
本研究通过多成分、多靶点、多途径相互作用，揭示了 GBL 治疗 VD 的潜在分子机制，为 VD 的临床治疗和先导药物开发提供了理论依据。
