Exploring the Mechanism of Therapeutic Effects of Polydatin in Lung Ischemia-Reperfusion Injury by Network Pharmacology and Experiment Validation
Year: 2026
Type: article
Abstract: Congcong Zhang, Yixin Wang, Haidong Tang, Zhiyi Wu, Shu Jia, Jingyi Wu, Xiaomin Yao Department of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, People’s Republic of ChinaCorrespondence: Xiaomin Yao, Department of Pharmacy, Zhejiang Pharmaceutical University, No. 888, Yinxian Avenue, Yinzhou District, Ningbo, Zhejiang Province, People’s Republic of China, Email [email protected]: To elucidate the therapeutic mechanism of polydatin against lung ischemia-reperfusion injury (LIRI), this study adopted an integrated strategy combining network pharmacology with experimental verification.Methods: Potential targets of polydatin were retrieved from TCMSP, PubChem, SwissTargetPrediction, and Herb. LIRI-related targets were were collected from GeneCards, OMIM, and TTD. Venn analysis was used to identify common targets. A protein–protein interaction (PPI) network was constructed using STRING and analyzed with Cytoscape (CytoNCA plugin).Enrichment analyses (GO/KEGG) were performed to identify key pathways. For experimental validation, an in vitro LIRI model was established in human alveolar epithelial A549 cells undergoing hypoxia/reoxygenation (H/R). The protective effects and associated mechanisms of polydatin were then evaluated through multiple assays, including CCK-8 assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), ELISA, TUNEL staining, and reactive oxygen species (ROS) detection. Meanwhile, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were quantified.Results: Network pharmacology identified 199 potential common targets, with top 10 core ones including AKT1, IL6, TNF, ALB, TP53, INS, IL1B, STAT3, EGFR, and BCL2. GO/KEGG analyses indicated polydatin’s protective effects may relate to inflammatory response modulation, apoptotic signaling regulation, and NF-κB pathway involvement. Experimentally, polydatin enhanced H/R-injured A549 cell viability, reduced apoptosis, increased SOD activity, and decreased MDA, ROS, and inflammatory cytokines (IL-6, IL-1β, TNF-α). It also upregulated AKT1 and ALB mRNA and downregulated TP53 mRNA.Conclusion: Collectively, our results indicate that polydatin alleviates LIRI by attenuating oxidative stress, inflammation, and apoptosis, likely via multi-target and multi-pathway mechanisms centered on key hubs such as AKT1, IL6, TNF, ALB, TP53, and the NF-κB pathway. This study provides a theoretical and experimental basis for further exploration of polydatin as a potential LIRI treatment. Keywords: polydatin, lung ischemia-reperfusion injury, network pharmacology, oxidative stress, inflammation, A549 cells
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7128653624
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