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image of Multi-Omics and Network Pharmacology Reveal Calycosin as a Candidate Metabolic Modulator in COPD

Abstract

Introduction

Despite the global burden of chronic obstructive pulmonary disease (COPD), its pathogenesis remains elusive, and current therapies fail to halt disease progression. Calycosin, a bioactive isoflavone from Traditional Chinese Medicine (TCM), exhibits anti-inflammatory and antioxidant properties, yet its therapeutic potential in COPD remains unexplored.

Methods

We integrated transcriptomic data of human lung tissue from the Gene Expression Omnibus (GEO) database (GSE8581) and human serum metabolomic data from a published research paper to identify COPD-associated pathways. Network pharmacology, including target screening, analysis, and molecule docking, was employed to elucidate the mechanisms of calycosin for COPD therapy.

Results

Multi-omics analysis revealed significant activation of the pyruvate metabolism pathway and glyoxylate/dicarboxylate metabolism pathway in COPD patients, with 590 differentially expressed genes (DEGs) and 116 differentially expressed metabolites (DEMs) identified. Calycosin targets six key regulators (NME1, ALDH2, PGAM1, LDHA, PCNA, RASD1) with binding affinities (−5.1 to −10.2 kcal/mol) validated molecular docking, implicated in these pathways.

Discussion

This study bridges TCM-derived natural products with modern omics-driven drug discovery, revealing calycosin as a promising COPD intervention by targeting metabolic hubs to mitigate inflammation and metabolic dysfunction, and pioneering an integrated multi-omics and network pharmacology framework for elucidating TCM mechanisms. However, the lack of direct experimental validation in COPD models and the use of data from different biological sources limit the extrapolation of the results. Further in vitro and in vivo experiments are needed.

Conclusions

This integrated analysis highlights distinct metabolic pathway perturbations, specifically in pyruvate and glyoxylate/dicarboxylate metabolism, as key components of COPD pathophysiology and proposes calycosin as a mechanistically grounded candidate for modulating these pathways. This work shifts focus towards metabolic dysregulation as a central therapeutic target, providing a foundation for developing novel strategies to manage COPD beyond symptom control.

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2025-05-19
2026-01-29

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Multi-Omics and Network Pharmacology Reveal Calycosin as a Candidate Metabolic Modulator in COPD
Bentham Science Publishers ; https://doi.org/10.2174/0113862073402760250516120303
/content/journals/cchts/10.2174/0113862073402760250516120303
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  • Article Type:     Research Article
Keywords: molecule docking ; transcriptomics ; COPD ; Calycosin ; network pharmacology ; metabolomics ; pyruvate metabolism

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