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

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-01-01 DOI:10.1016/j.phymed.2024.156280

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.

Abstract Image

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清肺饮通过促进完全自噬抑制坏死坏死来缓解肺炎链球菌肺炎。

背景：细菌性肺炎是所有肺炎类型中最常见的，以肺炎链球菌为主要病原体。清肺饮是临床治疗细菌性肺炎常用的中药方剂。既往研究证实了芪fy治疗肺炎链球菌肺炎的多靶点和疗效特点。目的：本研究的目的是探讨芪fy治疗肺炎链球菌肺炎的作用机制。方法：首先建立小鼠肺炎链球菌感染的体内模型，采用苏木精-伊红（HE）染色法和支气管肺泡灌洗液细胞因子水平测定法评价芪清注射液的疗效。接下来，单细胞转录组学被用于鉴定受QFY影响的靶细胞亚型、信号通路和生物学过程。最后，通过western blot分析、免疫荧光（IF）、吖啶橙（AO）染色和碘化丙啶（PI）染色，对溶气素（PLY）诱导的小鼠肺上皮细胞（TC-1）体外模型进行验证。结果：芪fy在体内可减轻肺部炎症，降低支气管肺泡灌洗液中TNF-α、IL-6水平。使用单细胞转录组学对113,353个细胞进行了分类，鉴定了12种主要细胞类型。通过单细胞转录组学证实，QFY主要靶向肺上皮细胞。差异表达基因被证明在自噬和坏死坏死信号通路中富集，并鉴定出关键的差异表达基因Sequestosome 1 （p62/SQSTM1）。结果显示，PLY可诱导TC-1细胞依赖ripk1的坏死坏死和不完全自噬。QFY被证明通过下调p62的表达，从而降低RIPK1和MLKL的磷酸化，促进完全自噬，减轻肺炎链球菌诱导的肺上皮细胞死亡的坏死。结论：本研究证实芪散能有效缓解肺炎链球菌肺炎。其作用机制可能是通过下调p62表达促进完全自噬，从而减轻肺炎链球菌诱导的肺上皮细胞坏死，减轻肺损伤。为临床防治肺炎链球菌肺炎提供科学依据。

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来源期刊

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.