Treatment with Number 2 Feibi Recipe, a Compound Traditional Chinese Medicine Reduces Bleomycin-induced Pulmonary Fibrosis in Mice

Qi Long,Zhao Heng Liu,Jie Niu,Xiao Feng Gu,Fang Cao,Yang Jiao,Hao Ge Liu,Qing Lu Pang

doi:10.11648/j.cmr.20211003.13

Abstract

Objective: Oxidative stress with reactive oxygen species (ROS) generated from exogenous oxidants and pollutants exposure is involved in the pathogenesis of Idiopathic pulmonary fibrosis (IPF). Number 2 Feibi Recipe (Number 2 FBR) is a traditional Chinese herbal formula which can attenuate the lung injury induced by PM2.5. The present study is to explore the effect and mechanism of Number 2 FBR on bleomycin (BLM)-induced pulmonary fibrosis in C57BL/6Cnc mice. Method: Bleomycin-induced C57BL/6Cnc mice were treated with Number 2 FBR and Sulforphane for two weeks. HE and Masson trichrome staining were performed to evaluate pathological changes in lung tissues. The extent of lung fibrosis was evaluated with fibrosis scores, collagen volume fraction, and hydroxyproline concentration. Levels of SOD and 8-iso-PGF2α in lung tissues were measured by using commercial assay kits. The levels of Nrf2, SOD, GSH-Px, and TGF-β1 relative protein and mRNA in lung tissues were measured by real time PCR and Western blot respectively. Results: The results showed that Number 2 FBR ameliorated bleomycin-induced pathological changes, collagen deposition and significantly decreased fibrosis scores, collagen volume fraction, and hydroxyproline concentration in the mice lungs. Additionally, Number 2 FBR inhibited the expression of 8-iso-prostaglandin F2α (8-iso-PGF2α) and transforming growth factor beta1 (TGF-β1), and increased the expression of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in lung tissues. Conclusion: Number 2 FBR has an effect of anti-fibrosis by regulating the lung oxidants and antioxidants balance.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, fibrotic interstitial lung disease with a median survival time between 3-5 years from diagnosis and limited therapeutic options [1]
Compared with the normal control group, obvious alveolar structural disorder, abnormal thickening of the alveolar wall, massive deposition of matrix, amount of blue collagen fibers, and fibroblasts appeared in the model group after the BLM intratracheal instillation
Compared with the model group, the lung injury and fibrosis induced by BLM were reduced to varying degrees in both sulforphane and Number 2 FBR groups

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, fibrotic interstitial lung disease with a median survival time between 3-5 years from diagnosis and limited therapeutic options [1]. The promotion of pulmonary fibrosis by oxidative stress involves multiple mechanisms that include (i) causing extensive modifications and damage to macromolecules (e.g., DNA, lipids, proteins), and trigger the generation of peroxidation products (e.g., DNA adducts, lipid peroxides) further promoting the cycle of alveolar damage and abnormal repair [11,12,13], (ii) results in an acute accumulation of inflammatory cells in the alveolar spaces and interstitium through the activation of nuclear factor-kappa B (NF-κB) [14, 15], (iii) promote alveolar epithelial cell apoptosis through mitochondrial-mediated intrinsic pathways or death receptor-mediated extrinsic pathways [16], (iv) directly contribute to profibrotic activation of TGF-β, initiating a positive feedback loop of TGF-β1 activation with resultant persistent fibrosis [17, 18], (v) promote apoptosis resistance of myofibroblasts leading to their accumulation [19], (vi) activate matrix metalloproteinases (MMPs), increasing their transcription, deactivating proteases, and subsequent collagen deposition [20, 21]

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Discussion

Conclusion