Work

Rg1-R1 attenuates cardiac ischemia/reperfusion-induced endothelial cell injury through activating the ULK1/PGAM5-FUNDC1-mitophagy pathway

Year: 2025

Type: article

Abstract: Background: Mitochondrial dysfunction has been recognized as a pivotal pathological mechanism underlying myocardial ischemia/reperfusion injury (MIRI).Ginsenoside Rg1 and notoginsenoside R1 exhibits cardioprotective effects against MIRI. However, their molecular mechanisms remain unclear. This study aims to investigate the therapeutic potential of Rg1 and R1 in ameliorating cardiomyocyte injury through mitophagy regulation, with a focus on elucidating the molecular crosstalk between these compounds and key mitophagy-related signaling pathways. Methods: Cardiac injury in mice was induced by subjecting the heart to 45 min of ischemia followed by 6 h of reperfusion. Post-injury, the mice were treated with intraperitoneal injections of Rg1-R1. The effects of Rg1-R1 on MIRI were assessed through electrocardiography, echocardiography, HE/Masson staining, and Transmission Electron Microscope. The impact of Rg1-R1 on biochemical markers of myocardial injury was also analyzed. Cardiac microvascular endothelial cells (CMECs) were pretreated with Rg1-R1 prior to being exposed to hypoxia/reoxygenation (H/R). Subsequently, cellular function and mitochondrial function were evaluated. Results: Our results indicated that in vivo, Rg1-R1 improved MIRI-induced cardiac dysfunction; in vitro, exposure of CMECs to Rg1-R1 reduced H/R injury severity and protected mitochondria. Further studies illustrated the protective effect of Rg1-R1 achieved via the regulation of FUNDC1-mediated mitophagy. In addition, we found that Rg1-R1 exerted these protective effects by activating FUNDC1-dependent mitophagy through the ULK1/PGAM5 pathway. Conclusions: Our results indicated that Rg1-R1 attenuates MIRI-induced endothelial cell injury through activating the ULK1/PGAM5-FUNDC1-mitophagy pathway, and may represent a novel therapeutic target in the context of MIRI.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2025.100973

Authors: Xiayinan Song, Jinlan Deng, Danyang Wang, Zhenzhen Zheng, Chao Li, Jie Li

Institutions: Shandong University of Traditional Chinese Medicine, Dalian University, Affiliated Zhongshan Hospital of Dalian University

Language: English

Topic: Ginseng Biological Effects and Applications

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Natural Science Foundation of China