Pterostilbene attenuates lung ischemia-reperfusion injury: integrative insights from network pharmacology, molecular dynamics, and experimental validation

作者：Haotian Bai, Hongyun Zhao, Jinteng Feng, Hongyi Wang, Yan Li, Zhe Chen, Bin He, Chi Chiu Wang, Rui Gao, Rui Zhao, Shan Gao, Guangjian Zhang · 发表于：Frontiers in Pharmacology · 年份：2026 · DOI：10.3389/fphar.2026.1747977 · 被引用次数：1 · 研究领域：Sirtuins and Resveratrol in Medicine、Transplantation: Methods and Outcomes、Mitochondrial Function and Pathology

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 ...