Journal Article

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

Liu, Shuchen, Zhu, Xiaoxia, Meng, Zhiyun, Liu, Huimeng, Liang, Di, Han, Peng, Liu, Mingqiu, Gan, Hui, Liu, Taoyun, Wu, Zhuona, Dou, Guifang, Chen, Guangrui, Zhou, Huiyu, Gu, Ruolan, Li, Jian

2023

Overview

Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Apoptosis / Bleomycin / cepharanthine / Collagen / Collagen - metabolism / Coronaviruses / COVID-19 / COVID-19 - metabolism / Drug dosages / Extracellular matrix / FDA approval / Fibroblasts / Fibroblasts - metabolism / Growth factors / Inflammation / Inflammation - metabolism / Lung / Medical prognosis / myofibroblast / Myofibroblasts - metabolism / NF-kappa B - metabolism / NF-κB/NLRP3 / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / Pathogenesis / Proteins / Pulmonary fibrosis / Pulmonary Fibrosis - chemically induced / Pulmonary Fibrosis - drug therapy / Pulmonary Fibrosis - metabolism / Rats / Transforming Growth Factor beta1 - metabolism