Drug Design, Development and Therapy (Aug 2023)
Network Pharmacology and Molecular Docking Reveal the Mechanism of Isodon ternifolius (D. Don) Kudo Against Liver Fibrosis
Abstract
Jiasheng Deng,1,* Le Qin,2,* Zhipin Zhou3,* 1School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 3Department of Pharmacy, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhipin Zhou, Department of Pharmacy, Liuzhou People’s Hospital, 8 Wenchang Road, Cheng Zhong District, Liuzhou, Guangxi, People’s Republic of China, Tel +86 − 18776921947, Email [email protected]: Many studies have demonstrated the hepatoprotective or anti-fibrotic effects of Isodon ternifolius, 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.Methods: The chemical components of Isodon ternifolius were identified by literatures. Potential targets of Isodon ternifolius were predicted by Swiss Target Prediction. The disease targets were collected through the databases of Gene Card. Common targets of Isodon ternifolius 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.Results: 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 Isodon ternifolius, which showed that a multitude of ingredients of Isodon ternifolius were able to bind to the above target proteins, especially 2α-hydroxy oleanolic acid and (-)-Lambertic acid. Our experimental validation results showed that Isodon ternifolius inhibited the activation of PI3K-Akt and ERK1/2 signaling pathways.Conclusion: Through a network pharmacology approach and in vitro cell assay, we predicted and validated the active compounds of Isodon ternifolius and its potential targets for LF treatment. The results suggest that the mechanism of Isodon ternifolius treating LF by inhibiting angiogenesis may be related to the ERK1/2 and PI3K/Akt signaling pathways.Keywords: Chinese medicine, Isodon ternifolius (D. Don), network pharmacology, molecular docking, signaling pathway, liver fibrosis
