Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin.

Xiaozhou Sun,Wenxiu Qi,Lizhong Ding,Liwei Sun,Yan Xu,Li Liu,Zhongtian Wang,Daqing Zhao,Liping Sun,Changsheng Cui,Dandan Wang,Chengcheng Yin

doi:10.3389/fphar.2021.763160

Abstract

QingFei Yin (QFY), a Chinese traditional medicine recipe, is known for its excellent therapeutic pharmacological effects for the treatment of bacterial lung infections, although its molecular mechanism of action remains unknown. Here, QFY chemical composition was determined using a High-Performance Liquid Chromatography-Mass (HPLC-MS/MS)-based method then QFY was evaluated for protective pharmacological effects against pneumonia using two models: a Streptococcus pneumoniae-induced in vivo mouse model and an in vitro pneumolysin (PLY)-induced murine lung alveolar-derived MH-S cell line-based model. Notably, QFY exerted prominent anti-pneumonia effects both in vivo and in vitro. To further explore QFY protective effects, 4D label-free proteomics analysis, pathologic evaluation, and immunohistochemical (IHC) analysis were conducted to identify cellular pathways involved in QFY protection. Notably, our results indicated that NF-κB/NLRP3 and autophagy pathways may contribute to pharmacological effects associated with QFY-based protection. Briefly, QFY triggered autophagy via down-regulation of upstream NLRP3/mTOR signaling pathway events, resulting in the amelioration of inflammatory injury. Collectively, our results revealed molecular mechanisms underlying QFY protection against pneumonia as a foundation for the future development of novel treatments to combat this disease and reduce antibiotic abuse.

Highlights

Pneumonia, a type of acute lower respiratory infection, accounts for an extremely large proportion of the overall worldwide disease burden (Rudan et al, 2008; D 2016 Lower Respirator, 2018; Bernstein, 1999)
To further explore whether Qing Fei Yin (QFY) protective alleviation of S.pn infection was associated with NLRP3 down-regulation, we investigated expression levels of key proteins within PLY-treated MH-S cells
QFY exerts prominent anti-pneumonia effects both in a S.pn-induced in vivo mouse model and an in vitro PLYstimulated MH-S cell-based model

Summary

Introduction

A type of acute lower respiratory infection, accounts for an extremely large proportion of the overall worldwide disease burden (Rudan et al, 2008; D 2016 Lower Respirator, 2018; Bernstein, 1999). Streptococcus pneumoniae (S.pn), a gram-positive bacterium, is recognized as the most common cause of pathogen-induced pneumonia, while causing respiratory tract infections, pulmonary parenchymal inflammation, and pulmonary infection-derived bacteremia (D 2016 Lower Respirator, 2018; Bernstein, 1999). Such dire pathological effects have been shown to involve the. Traditional Chinese medicines (TCM) as alternative treatments have been attracting increasing attention around the world, due to their long history of clinical use and proven therapeutic pharmacological effects for alleviating infectious diseases (Qiu et al, 2012; Chen et al, 2015; Yang et al, 2017; Gong et al, 2020; Zhang et al, 2020). The molecular mechanism underlying QFY alleviation of pneumonia remains unclear

Methods

Results

Conclusion