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

Abstract

AimsThis 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 methodsThe 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 in vitro 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 findingsSix candidate targets were predicted based on network pharmacology and molecular docking, namely PIK3CA, PDPK1, RAC1, PTK2, KDR, and RPS6KB1. 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 PIK3CA and KDR (P < 0.001). Dex up-regulated the mRNA expression of PDPK1 and RAC1, while Tet (1.25 μΜ) down-regulated (P < 0.001). Dex up-regulated the mRNA expression of PTK2, but Tet had no effect. Dex down-regulated RPS6KB1 mRNA expression, while Tet (5 μΜ) up-regulated (P < 0.01). SignificanceCombined 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 PDPK1 and RAC1. The results of this study will provide scientific reference for the prevention and clinical diagnosis and treatment of PF.