Network Pharmacology and Molecular Docking Reveal the Mechanism of (D. Don) Kudo Against Liver Fibrosis.

AIM

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.

METHODS

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.

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 , 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.

CONCLUSION

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.