グリチルレチン酸はNrf2経路を介して慢性心不全を改善する

To explore the mechanism by which glycyrrhetinic acid (GA) alleviates chronic heart failure (CHF), focusing on NR3C1-mediated regulation of Nrf2 and oxidative stress.

A CHF rat model was established via transverse aortic constriction and treated with GA or NR3C1 knockdown. Cardiac function, hypertrophy, fibrosis, and oxidative stress markers were evaluated. In vitro, H9c2 cells were treated with isoproterenol to mimic CHF and subjected to GA, Nrf2 inhibitor, or NR3C1 modulation. Gene/protein expression, ROS, GSH, MDA, and mitochondrial membrane potential were assessed. Regulatory interactions between NR3C1 and Nrf2 were examined using luciferase, ChIP-qPCR, and CHX assays.

GA alleviated myocardial hypertrophy and fibrosis in CHF rat models. GA also suppressed oxidative stress in CHF cell models. GA upregulated Nrf2 and its downstream target HO-1 at the protein level. NR3C1 was identified as a key upstream regulator of Nrf2, promoting its protein stability. NR3C1 knockdown decreased Nrf2 and HO-1 protein expression, disrupted mitochondrial membrane potential, and weakened the protective effects of GA against oxidative stress and cardiac dysfunction both in vitro and in vivo.

GA alleviates CHF by enhancing NR3C1-mediated stabilization of Nrf2 and reducing oxidative stress.