Dehydrocorydaline attenuates myocardial ischemia-reperfusion injury via the FoXO signalling pathway: A multimodal study based on network pharmacology, molecular docking, and experimental study

作者：Hongzheng Li, Wenwen Yang, Zucheng Shang, Yingdong Lu, Aling Shen, Daxin Chen, Guosheng Lin, Mengfan Li, Renfeng Li, Meizhu Wu, Zhi Guo, Hua Qu, Changgeng Fu, Zikai Yu, Keji Chen · 发表于：Journal of Ethnopharmacology · 年份：2024 · DOI：10.1016/j.jep.2024.118738 · 被引用次数：14 · 研究领域：FOXO transcription factor regulation、Berberine and alkaloids research、Medicinal Plants and Bioactive Compounds

ETHNOPHARMACOLOGICAL RELEVANCE: Dehydrocorydaline (DHC), an active component of Corydalis yanhusuo (Y.H. Chou & Chun C. Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu (Papaveraceae), exhibits protective and pain-relieving effects on coronary heart disease, but the underlying mechanism still remains unknown. AIM OF THE STUDY: Network pharmacology and experimental validation both in vivo and in vitro were applied to assess whether DHC can treat myocardial ischemia-reperfusion injury (MIRI) by regulating the forkhead box O (FoxO) signalling pathway to inhibit apoptosis. MATERIALS AND METHODS: DHC and MIRI targets were retrieved from various databases. Molecular docking and microscale thermophoresis (MST) determined potential binding affinity. An in vivo mouse model of MIRI was established by ligating the left anterior descending coronary artery. C57BL/6N mice were divided into sham, MIRI, and DHC (intraperitoneal injection of 5 mg/kg DHC) groups. Haematoxylin and eosin, Masson, and immunohistochemical stainings verified DHC treatment effects and the involved signalling pathways. In vitro, H9c2 cells were incubated with DHC and underwent hypoxia/reoxygenation. TUNEL, JC-1, and reactive oxygen species stainings and western blots were used to explore the protective effects of DHC and the underlying mechanisms. RESULTS: Venny analysis identified 120 common targets from 121 DHC and 23,354 MIRI targets. DHC exhibited high affinity for CCND1, CDK2, and MDM2 (<-7 kcal/mol). In vivo, DHC attenuated...