Ginsenoside Rb1 attenuates coronary microvascular inflammatory injury via NDUFS4-SIRT5-DUSP1-mediated mitochondrial quality control in a murine ischemia-reperfusion model

Abstract

Ginsenoside Rb1 is a prominent bioactive component in traditional Chinese medicine. This study investigated the molecular mechanisms underlying the protective effects of Ginsenoside Rb1 on endothelium during ischemia-reperfusion (I/R) injury. To enrich for marker genes and investigate the differential expression of DUSP1 and NDUFS4 in coronary artery disease, single-cell transcriptome sequencing was utilized. SIRT5 CKO/TG and NDUFS4 CKO/TG mouse models were established using gene modification techniques. Si-DUSP-1/ad-DUSP-1 and si-SIRT5/ad-SIRT5 cell models were constructed. Fluorescence detection, mitochondrial membrane potential assays, RT-PCR, and Western blotting were employed to detect the mitochondrial function. NDUFS4 and DUSP1 regulate the mitochondrial unfolded protein response (mtUPR), energy metabolism, and dynamics, and may be crucial regulatory genes in the development of coronary artery disease. Ginsenoside Rb1 modulates the NDUFS4-SIRT5-DUSP1 axis, regulates the mitochondrial quality control network, and alleviates coronary microvascular inflammatory injury. Ginsenoside Rb1 regulates the NDUFS4-SIRT5-DUSP1 axis, modulating the mitochondrial quality control network, inhibiting the inflammatory cascade response, and improved myocardial function. • Expression interactions between SIRT5, DUSP1, and NDUFS4 co-regulate the mitochondrial quality monitoring network. • Ginsenoside Rb1 regulates NDUFS4-SIRT5-DUSP1-mediated mitochondrial quality monitoring and inflammatory crosstalk to improve coronary microvascular ischemia-reperfusion injury.