Ginsenoside Ro Targets BCAT1/2 to Suppress Ferroptosis: A Novel Therapeutic Strategy for Ischemic Cardioprotection

Ginsenoside Ro, a compound with diverse therapeutic potential, has yet to be explored for its role in myocardial ischemia (MI). Our study employed murine MI models, induced by coronary artery ligation and isoproterenol administration, alongside oxygen glucose-deprivation-injured neonatal rat ventricular myocytes, aiming to reveal the effects of Ro in MI injury and elucidate the underlying mechanisms. These findings demonstrated that Ro significantly enhanced cardiac function, mitigated histopathological damage, and reduced the level of apoptosis. Mechanistically, Ro directly targeted branched-chain aminotransferases 1 and 2 (BCAT1 and BCAT2), augmented enzyme activities, and expression of BCAT1/2, thereby activating the Keap1/Nrf2/HO-1 pathway to suppress cardiac ferroptosis. Furthermore, inhibition of BCAT1/2 effectively abolished Ro's cardioprotective effects. This study not only identifies BCAT1/2 as novel molecular targets of Ro but also reveals a previously unrecognized mechanism for suppressing ferroptosis. These findings underscore Ro's potential as a promising BCAT1/2 agonist and therapeutic candidate for MI, offering new insights into cardiovascular protection and highlighting its clinical significance.