Maiwei Yangfei decoction protects against pulmonary fibrosis by suppressing NLRP3 inflammasome-mediated pyroptosis of alveolar macrophage

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-05 DOI:10.1016/j.phymed.2025.157041

Dongwei Zhu , Qi Zhao , Tingyu Pan , Le Bai , Yisheng Zhao , Jing Wang , Zhichao Wang , Yong Xu , Xianmei Zhou

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引用次数: 0

Abstract

Background

Pulmonary fibrosis (PF) is a progressive and irreversible pathological manifestation of fibrotic interstitial lung diseases, characterized by chronic inflammation, excessive extracellular matrix (ECM) deposition, and architectural distortion of lung parenchyma, ultimately leading to respiratory failure. Maiwei Yangfei Decoction (MWYF) has been clinically applied in PF treatment, and can effectively improve the lung function and life quality of PF patients. Nevertheless, the precise regulatory mechanisms underlying its anti-fibrotic effects require further investigation.

Purpose

To investigate MWYF's pharmacological action and potential mechanism against PF.

Methods

Firstly, a PF mouse model was established by intratracheal nebulization of bleomycin (BLM). The effect of MWYF on PF was evaluated through micro-CT imaging and histopathological analysis. Subsequently, transcriptomics and proteomics were employed to investigate the crucial mechanism underlying the anti-fibrotic effects of MWYF. Immunofluorescence (IF), ELISA, TEM, SEM, Western blot (WB), and qPCR were then conducted to validate the inhibitory effects of MWYF on alveolar macrophages (AM) pyroptosis both in vivo and in vitro. Finally, the NLRP3 inhibitor (MCC950) was applied in MH-S cells to investigate the impact of MWYF on NLRP3 inflammasome.

Results

MWYF exhibited significant efficacy against BLM-induced PF. Integrated transcriptomic and proteomic analyses suggested that NLRP3 inflammasome-mediated pyroptosis intrinsically participated in the anti-fibrotic effects of MWYF. Further in-vivo experiments confirmed that MWYF alleviated AM pyroptosis in lung tissues via modulating the assembly of the NLRP3 inflammasome. In vitro, MWYF inhibited LPS plus Nigericin-induced pyroptosis in MH-S cells, as well as primary mouse lung fibroblast (PMLF) proliferation, activation, and ECM secretion, by suppressing NLRP3 inflammasome activation.

Conclusion

This study illustrated that MWYF alleviated PF by inhibiting NLRP3 inflammasome-mediated AM pyroptosis by integrating multi-omics approaches, indicating that MWYF had promising clinical translational potential in PF therapy.

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麦味养肺汤通过抑制NLRP3炎症小体介导的肺泡巨噬细胞焦亡而预防肺纤维化

肺纤维化（pulmonary fibrosis， PF）是肺纤维化间质性疾病的一种进行性、不可逆的病理表现，以慢性炎症、细胞外基质（extracellular matrix， ECM）过度沉积、肺实质结构扭曲为特征，最终导致呼吸衰竭。麦味养肺汤（MWYF）已被临床应用于PF治疗，可有效改善PF患者的肺功能和生活质量。然而，其抗纤维化作用的确切调控机制需要进一步研究。目的探讨百维灵对PF的药理作用及可能机制。方法首先采用气管内雾化博来霉素（BLM）建立PF小鼠模型。通过显微ct成像和组织病理学分析评估MWYF对PF的影响。随后，转录组学和蛋白质组学被用于研究MWYF抗纤维化作用的关键机制。然后通过免疫荧光（IF）、ELISA、TEM、SEM、Western blot （WB）和qPCR验证MWYF对肺泡巨噬细胞（AM）焦亡的体内外抑制作用。最后，将NLRP3抑制剂（MCC950）应用于MH-S细胞，研究MWYF对NLRP3炎性体的影响。结果smwyf对blm诱导的PF具有显著的抗纤维化作用，综合转录组学和蛋白质组学分析表明NLRP3炎症小体介导的焦亡本质上参与了MWYF的抗纤维化作用。进一步的体内实验证实，MWYF通过调节NLRP3炎性体的组装来减轻肺组织AM焦亡。在体外，MWYF通过抑制NLRP3炎性体的激活，抑制LPS +尼日利亚菌素诱导的MH-S细胞的焦亡，以及原代小鼠肺成纤维细胞（PMLF）的增殖、活化和ECM的分泌。结论MWYF通过整合多组学方法，通过抑制NLRP3炎症小体介导的AM焦亡来缓解PF，表明MWYF在PF治疗中具有良好的临床转化潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.