School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, People's Republic of China.
Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People's Republic of China.
Drug Des Devel Ther. 2023 Aug 7;17:2335-2351. doi: 10.2147/DDDT.S412818. eCollection 2023.
Many studies have demonstrated the hepatoprotective or anti-fibrotic effects of , but its pharmacological basis and mechanism remain unclear. In this study, we used in vitro models to validate the predicted results and revealed the potential mechanism of action and active ingredients through network pharmacology methods and molecular docking.
The chemical components of were identified by literatures. Potential targets of were predicted by Swiss Target Prediction. The disease targets were collected through the databases of Gene Card. Common targets of and liver fibrosis were obtained by online tool Venny 2.1. PPI protein interaction network was obtained using String database, and target protein interaction network was drawn using Cytoscape software. Signaling pathway enrichment analysis was performed on drug-disease targets with of DAVID database.
Twenty-one potential active ingredients and 298 potential targets were predicted by Swiss Target Prediction platform. Ninety pathways related to liver fibrosis were obtained by KEGG enrichment. The TLR4, MAPK and PI3K-Akt signaling pathways are mostly associated with liver fibrosis. Molecular docking techniques were used to validate the core target proteins TNF, Akt1, MAPK1, EGFR and TLR4 binding to the ingredients of , which showed that a multitude of ingredients of were able to bind to the above target proteins, especially 2α-hydroxy oleanolic acid and (-)-Lambertic acid. Our experimental validation results showed that inhibited the activation of PI3K-Akt and ERK1/2 signaling pathways.
Through a network pharmacology approach and in vitro cell assay, we predicted and validated the active compounds of and its potential targets for LF treatment. The results suggest that the mechanism of treating LF by inhibiting angiogenesis may be related to the ERK1/2 and PI3K/Akt signaling pathways.
许多研究表明[药物名称]具有保肝或抗纤维化作用，但其药理基础和机制尚不清楚。本研究通过体外模型验证了预测结果，并通过网络药理学方法和分子对接揭示了其潜在的作用机制和活性成分。
通过文献鉴定[药物名称]的化学成分。使用 Swiss Target Prediction 预测[药物名称]的潜在靶点。通过 Gene Card 数据库收集疾病靶点。通过在线工具 Venny 2.1 获得[药物名称]和肝纤维化的共同靶点。使用 String 数据库获得 PPI 蛋白相互作用网络，并使用 Cytoscape 软件绘制目标蛋白相互作用网络。使用 DAVID 数据库对药物-疾病靶点进行信号通路富集分析。
通过 Swiss Target Prediction 平台预测得到 21 种潜在活性成分和 298 个潜在靶点。KEGG 富集得到 90 条与肝纤维化相关的通路。TLR4、MAPK 和 PI3K-Akt 信号通路与肝纤维化关系最为密切。分子对接技术验证了 TNF、Akt1、MAPK1、EGFR 和 TLR4 与[药物名称]中成分的核心靶蛋白结合，结果表明[药物名称]的多种成分能够与上述靶蛋白结合，特别是 2α-羟基齐墩果酸和（-）-拉伯替酸。我们的实验验证结果表明，[药物名称]抑制了 PI3K-Akt 和 ERK1/2 信号通路的激活。
通过网络药理学方法和体外细胞实验，预测和验证了[药物名称]治疗 LF 的活性化合物及其潜在靶点。结果表明，[药物名称]通过抑制血管生成治疗 LF 的机制可能与 ERK1/2 和 PI3K/Akt 信号通路有关。
