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Updated: Apr 18, 2026
Author Spotlight: Insights into the Effect of Ischemia Reperfusion on Lung Transplantation
Published on: April 12, 2024
Pterostilbene attenuates lung ischemia-reperfusion injury: integrative insights from network pharmacology, molecular
Haotian Bai1,2, Heng Zhao1,2, Jinteng Feng1,2
1Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Background:
Lung ischemia-reperfusion injury (LIRI) is a principal cause of primary graft dysfunction (PGD) following lung transplantation, severely compromising recipient survival. However, effective therapies remain unavailable due to its complex pathophysiology. Pterostilbene (PTE) is a natural stilbene compound known for its well-documented anti-inflammatory, antioxidant, and antitumor properties. However, its effects and underlying mechanisms in LIRI remain unclear.
Methods:
Potential targets of PTE and LIRI were retrieved from multiple public databases, followed by network analysis and functional enrichment to identify core targets and pathways. Molecular docking and dynamics simulations were conducted to assess the binding affinity and stability between PTE and its core targets. Finally, a rat left hilar clamping model and an OGD/R model in BEAS-2B cells were employed to experimentally validate the protective effects and molecular mechanisms of PTE.
Results:
A total of 104 intersecting targets were identified with ten core genes such as PIK3CB and MAPK8 highlighted. Gene Ontology and KEGG analyses revealed significant enrichment in apoptosis- and inflammation-related pathways, particularly PI3K/AKT and MAPK signaling. Docking and simulation results demonstrated stable binding of Pterostilbene to core targets (binding energy ≤-5.6 kcal/mol). In vivo, PTE alleviated IR-induced lung injury, reduced pulmonary edema, apoptosis, and pro-inflammatory cytokine release. In vitro, PTE enhanced cell viability, decreased the levels of pro-inflammatory cytokines, inhibited Caspase-3 activation and Bax expression, and increased Bcl-2 levels. Mechanistically, PTE promoted PI3K/AKT activation while suppressing JNK/c-Jun phosphorylation both in vivo and in vitro. Notably, LY294002 (a PI3K inhibitor) and Anisomycin (a JNK activator) partially reversed the anti-apoptotic and anti-inflammatory effects of PTE, respectively.
Conclusion:
This study provides the first integrated evidence combining network pharmacology and experimental validation that PTE protects against LIRI by modulating the PI3K/AKT and JNK/c-Jun signaling pathways, offering novel pharmacological insights into its translational potential in LIRI.
