ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Food Microbiology
This article is part of the Research TopicNew Insights in Multifunctional Foods: Applications of Postbiotics, Pharmabiotics, Psychobiotics, Parabiotics, and CobioticsView all 4 articles
Integrative Network Pharmacology, Transcriptomics, and Microbiomics Elucidate the Therapeutic Mechanism of Polygala tenuifolia Willd Water Extract in Chronic Obstructive Pulmonary Disease
Provisionally accepted
- Jilin University, Changchun, China
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Background: Polygala tenuifolia Willd (PT) is a plant with both medicinal and edible values. Traditionally, it has been used for sedation, enhancing cognition, resolving phlegm, and relieving cough. However, its protective effects and mechanisms against chronic obstructive pulmonary disease (COPD) remain unclear. Aim of the study: This study aims to observe the protective effects of the water extract of Polygala tenuifolia Willd (WEPT) on COPD, and to preliminarily elucidate its potential therapeutic mechanisms by integrating network pharmacology, molecular docking, multi-omics analysis, and molecular experiments. Methods and materials: HPLC quantified WEPT constituents. COPD mice models established via chronic smoke exposure underwent WEPT treatment, and the therapeutic effect was evaluated by lung function test, histopathology and cytokine profiling. Integrated multi-omics analyses (network pharmacology, transcriptomics, microbiomics) identified bioactive compounds, therapeutic targets, pathway regulations, and microbiota dynamics. Molecular docking validated compound-target interactions, while immunohistochemical/fluorescence assays confirmed key protein expression in lung tissues. Results: WEPT administration effectively reduced inflammatory cytokine levels in COPD mice, improved lung function, and alleviated histopathological damage like alveolar structural injury and airway inflammation. Network pharmacology and transcriptomic analyses identified Norhyoscyamine and Onjixanthone I as key active components, targeting PIK3CA and AKT1 via PI3K-AKT pathway regulation. Microbiome analysis showed WEPT restored gut microbiota balance. Molecular docking confirmed strong binding of bioactive compounds to core targets, while immunostaining assays demonstrated WEPT suppressed p-PI3K and p-AKT protein expression. Conclusion: WEPT may exert its intervention effects on COPD through a multi-target and multi-level comprehensive regulatory mechanism.
Keywords: Polygala tenuifolia Willd, Water extract, chronic obstructive pulmonary disease, Transcriptomics, Network Pharmacology, Gut Microbiota
Received: 15 Sep 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 An, Yu, Wang, Yu, Zheng and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hongqiang Lin, linhq@jlu.edu.cn
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