Qingfei Yin alleviates Streptococcus pneumoniae pneumonia by promoting complete autophagy to suppress necroptosis.

IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Tong Tian, Zhilong Xue, Xiaozhou Sun, Lizhong Ding, Renshuang Zhao, Zhongtian Wang, Jiaqi Wu, Xiao Li, Yiquan Li, Liping Sun
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引用次数: 0

Abstract

Background: Bacterial pneumonia is most prevalent among all pneumonia types, with Streptococcus pneumoniae being the main pathogen. Qingfei Yin (QFY) is a traditional Chinese medicine formula used in the clinical treatment of bacterial pneumonia. Previous studies have confirmed the multi-target and -effect characteristics of QFY in treating S. pneumoniae pneumonia.

Purpose: The purpose of this study was to explore the mechanism underlying QFY in treating pneumonia produced by S. pneumoniae.

Methods: First, an in vivo model of S. pneumoniae-induced pneumonia was established in mice and evaluated the efficacy of QFY by hematoxylin-eosin (HE) staining and measuring cytokine levels in bronchoalveolar lavage fluid. Next, single-cell transcriptomics was used to identify the targeted cell subtypes, signaling pathways, and biological processes affected by QFY. Finally, the findings were validated using a pneumolysin (PLY) -induced mouse lung epithelial cells (TC-1) model in vitro using western blot analysis, immunofluorescence (IF), acridine orange (AO) staining, and propidium iodide (PI) staining.

Results: QFY was shown to alleviate lung inflammation and reduce the TNF-α and IL-6 levels in bronchoalveolar lavage fluid in vivo. A total of 113,353 cells were classified using single-cell transcriptomics and 12 major cell types were identified. By single-cell transcriptomics, QFY was confirmed to primarily target lung epithelial cells. Differentially expressed genes were shown to be enriched in autophagy and necroptosis signaling pathways, and the key differentially expressed gene, Sequestosome 1 (p62/SQSTM1), was identified. PLY was shown to induce RIPK1-dependent necroptosis and incomplete autophagy in TC-1 cells. QFY was shown to promote complete autophagy by downregulating the expression of p62, thereby reducing phosphorylation of RIPK1 and MLKL, and alleviating necroptosis in S. pneumoniae-induced lung epithelial cell death.

Conclusion: This study demonstrated that QFY can effectively alleviate S. pneumoniae pneumonia. The mechanism of action may be that QFY promotes complete autophagy by downregulating p62 expression, thereby alleviating necroptosis of S. pneumoniae-induced lung epithelial cells and reducing lung injury. It provides a scientific basis for clinical prevention and treatment of S. pneumoniae pneumonia.

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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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