Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin Recipe
Qing-Fei Yin(QFY), a Chinese traditional medicine recipe, is known for its excellent therapeutic efficacy for the treatment of bacterial lung infections, although its molecular mechanism of action remains unknown. Here, QFY chemical composition was determined using the High Performance Liquid Chromatography-Mass(HPLC-MS/MS) method, and then QFY was evaluated for protective efficacy 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 pathways involved in QFY protection. Notably, pivotal roles for NLRP3 inflammasome and autophagy pathways were found to be pharmacologically important for QFY-based protection, with both pathways shown to reciprocally regulate one another. Briefly, QFY triggered autophagy via down-regulation of upstream NLRP3/mTOR signalling pathway events, resulting in quenching of the NF-κB pathway and amelioration of inflammatory injury. Collectively, our results reveal molecular mechanisms underlying QFY protection against pneumonia as a foundation for the future development of novel treatment therapy to combat this disease and reduce antibiotic abuse.
Xiaozhou Sun1*, Dandan Wang1, Lizhong Ding4 ,Yan Xu1, Wenxiu Qi3, Daqing Zhao3 ,Li Liu1, Cheng cheng Yin1, Changsheng Cui1, Zhongtian Wang1, Liwei Sun2*,LipingSun4*
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