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

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

doi:10.1016/j.phymed.2025.157041

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

Phytomedicine. 2025 Jul 5:145:157041. doi: 10.1016/j.phymed.2025.157041. Online ahead of print.

Authors

Dongwei Zhu¹, Qi Zhao¹, Tingyu Pan¹, Le Bai¹, Yisheng Zhao¹, Jing Wang¹, Zhichao Wang¹, Yong Xu², Xianmei Zhou³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
² School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: njzyyxuyong@163.com.
³ Department of Respiratory and Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: zhouxianmeijs@aliyun.com.

PMID: 40652799
DOI: 10.1016/j.phymed.2025.157041

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.

Keywords: Alveolar macrophage; Maiwei Yangfei Decoction; Proteomics; Pulmonary fibrosis; Pyroptosis; Transcriptomics.