Germacrone mitigates cardiac remodeling by regulating PI3K/AKT-mediated oxidative stress, inflammation, and apoptosis

Cardiac remodeling is a common consequence of cardiovascular diseases and is closely associated with oxidative stress, inflammation, and apoptosis. Germacrone, a bioactive compound present in Rhizoma curcuma, has been shown to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the protective effect of germacrone against cardiac remodeling. Here, C57BL/6 mice were subcutaneous injection with isoproterenol (ISO) once daily for two weeks and were concurrent intragastric injection of germacrone. In vitro, neonatal rat cardiomyocytes (NRCMs) were used to verify the protective effect of ger-macrone on ISO-induced cardiac injury. Our findings indicated that ISO induce oxidative stress, inflammation, and apoptosis in vivo and in vitro, while germacrone treatment significantly attenuates these effects, thereby attenuating myocardium remodeling and cardiac dysfunction. Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling.