Mechanistic Insights into the Effect of Yiqi Zishen Formula on Chronic Obstructive Pulmonary Disease: A Multiomics Integration Study

Abstract

Objective

This study was aimed to explore the prolonged therapeutic profile and underlying mechanisms of Yiqi Zishen Formula (YZF) in chronic obstructive pulmonary disease (COPD) management.

Methods

A COPD rat model was established through exposure to tobacco smoke and Klebsiella pneumoniae infections from weeks 1 to 8, followed by treatment with YZF from weeks 9 to 20. No treatment was administered from weeks 21 to 31. At week 32, all rats were euthanized, and lung tissue samples and blood specimens were collected for subsequent analyses. Then, comprehensive multiomics profiling—encompassing transcriptomics, proteomics, and metabolomics—was conducted to identify differentially expressed molecules in lung tissues and elucidate the underlying molecular mechanisms.

Results

By week 32, sustained therapeutic efficacy became apparent, characterized by diminished inflammatory cytokine expression, mitigation of protease–antiprotease dysregulation, and reduced collagen deposition. These differentially expressed molecules were predominantly enriched in pathways related to oxidoreductase activity, antioxidant homeostasis, focal adhesion, tight junction formation, adherens junction dynamics, and lipid metabolism regulation. Integrative analysis of predicted targets, transcriptomic, proteomic, and metabolomic datasets revealed that differentially expressed molecules in YZF-treated rats and YZF-targeted proteins collectively participated in lipid metabolism, inflammatory responses, oxidative stress, and focal adhesion pathways.

Conclusion

YZF provides sustained therapeutic benefits in COPD rat models, potentially through systemic regulation of lipid metabolism, inflammatory responses, oxidative stress, and focal adhesion pathways.

Keywords

chronic obstructive pulmonary disease - Yiqi Zishen Formula - multiomics profiling - system mechanism

CRediT Authorship Contribution Statement

Jiansheng Li: Conceptualization, funding acquisition, data curation, supervision, and writing-review & editing. Peng Zhao: Project administration, data curation, formal analysis, visualization and writing original draft. Yange Tian: Investigation, data curation, project administration, and writing-review & editing. Ya Li: Investigation, formal analysis, and software. Xuefang Liu: Investigation, data curation, and software.

Publikationsverlauf

Eingereicht: 12. März 2025

Angenommen: 17. Juni 2025

Artikel online veröffentlicht:
30. September 2025

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