Study on the molecular mechanisms of tetrandrine against pulmonary fibrosis based on network pharmacology, molecular docking and experimental verification.

AIMS

This study aims to screen the potential targets of tetrandrine (Tet) against pulmonary fibrosis (PF) based on network pharmacological analysis, molecular docking and experimental verification.

MAIN METHODS

The network pharmacology methods were employed to predict targets, construct Tet-PF-intersection target-pathway networks, and screen the candidate targets. The molecular docking was performed using AutoDockTools1.5.6. TGF-β1-induced human lung adenocarcinoma A549 cells were used as an experimental verification model, taking dexamethasone (Dex) as the positive control, to verify the effects of Tet on the mRNA expression of the candidate targets.

KEY FINDINGS

Six candidate targets were predicted based on network pharmacology and molecular docking, namely , and . The experimental verification results showed that Dex and Tet presented quite different pharmacological effects. Specifically, compared with the model group, both Dex and Tet (5 μΜ) significantly increased the mRNA expression of and ( < 0.001). Dex up-regulated the mRNA expression of and , while Tet (1.25 μΜ) down-regulated ( < 0.001). Dex up-regulated the mRNA expression of , but Tet had no effect. Dex down-regulated mRNA expression, while Tet (5 μΜ) up-regulated ( < 0.01).

SIGNIFICANCE

Combined with the results of theoretical calculation and experimental verification, and considering the roles of these targets in the pathogenesis of PF, Tet might antagonize PF by acting on and . The results of this study will provide scientific reference for the prevention and clinical diagnosis and treatment of PF.