Wenfei Buqi Tongluo Formula Against Bleomycin-Induced Pulmonary Fibrosis by Inhibiting TGF-β/Smad3 Pathway.

Daqing Zhao,Hongyu Qi,Ziyuan Wang,Lu Ding,Yingying Yang,Xiangyan Li,Wei Zhang,Yaxin Li,Jing Wang,Zeyu Wang,Jiachao Zhao,Linhua Zhao,Siyu Song

doi:10.3389/fphar.2021.762998

Abstract

Pulmonary fibrosis (PF) is the end stage of various chronic and progressive interstitial lung diseases. TGF-β, a profibrotic cytokine, can promote epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and fibroblast proliferation, which contribute to progressive lung remodeling in PF. The Wenfei Buqi Tongluo (WBT) formula has been certified to be effective in the prevention and treatment of PF in clinical practice and has inhibitory effects on EMT, inflammation, and profibrotic factors. However, the pharmacological mechanisms of WBT against PF need to be further explored. In this study, we first analyzed the chemical components of the WBT formula using the UHPLC/Q-TOF-MS analysis. The potential targets of the identified compounds from WBT were predicted by the network pharmacology, which was confirmed by in vivo and in vitro study. After screening by the PubChem database, we first identified the 36 compounds of WBT and predicted the TGF-β signaling pathway, with ECM degradation as potential mechanism of WBT against PF by the network pharmacology. Furthermore, WBT treatment inhibited the levels of TGF-β and Smad3 phosphorylation and subsequently alleviated EMT and ECM accumulation in the bleomycin-induced mouse model and TGF-β1–induced cell model. These findings indicate that WBT can block the progressive process of PF by inhibiting EMT and promoting ECM degradation via the TGF-β/Smad3 pathway. This study may provide new insights into the molecular mechanism of WBT for the prevention and treatment of PF in the clinical application.

Highlights

Pulmonary fibrosis (PF) is an end stage for various chronic and progressive interstitial lung diseases and is accompanied by gradually worsening symptoms such as fatigue, weight loss, and shortness of breath (King et al, 2011)
The 42 compounds in Wenfei Buqi Tongluo (WBT) were characterized by comparing the retention time, accurate mass, and fragment ions with those of the standards or data reported by the literature
The attribution to the single herb was confirmed by the base peak intensity (BPI) chromatograms of the blank sample, WBT formula, and individual herbs

Summary

Introduction

Pulmonary fibrosis (PF) is an end stage for various chronic and progressive interstitial lung diseases and is accompanied by gradually worsening symptoms such as fatigue, weight loss, and shortness of breath (King et al, 2011). IPF is a specific and common type of PF, in which lung function inexorably declines, leading to respiratory failure and eventually death. The incidence of IPF is increasing every year, with approximately three million people worldwide suffering from the disease (Nalysnyk et al, 2012; Hutchinson et al, 2015). Only two drugs, pirfenidone and nintedanib, are used for the treatment of IPF, which can slow the decline of lung function in patients with IPF (King et al, 2014; Flaherty et al, 2019). It is essential to develop drugs to delay the progression of IPF

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