Chrysin improves heart aging alteration in mice via modulating troponin/AGEs and targeting Sirt6/ Nrf2

Cardiovascular disease associated with aging is a vital issue with the worldwide increase in the elderly population. There is an urgent requirement for developing possible interventions activating cardiomyocytes survival such as Sirt and bloking AGE to prevent changes associated with cardiac aging.   The present work evaluated the cardioprotective effect of chrysin on D-galactose (D-gal) induced- heart aging in mice via modulating troponin /AGEs/ kinases and targeting the Sirt6/ Nrf2 signaling pathway. The mice were allocated randomly into four groups: Group 1: Normal control group. Group 2:  D-gal group (200 mg /kg/day; s.c) for 8 weeks to induce aging.  Groups 3& 4: chrysin (125 & 250 mg/kg; orally) concurrent with D-gal. Chrysin administration protected the heart against ECG changes in heart rate, ST height, QT, and QTc interval. Besides, it reduced troponin/creatine kinase and elevated PGC1α with a decrease in TNF-α, NF-κβ, and AGEs heart contents. In addition, chrysin exhibited upregulation of Sirt6/Nrf2 expression and alleviated myocardial degeneration, necrosis, and vacuolated myocytes induced by D-gal.Chrysin improves mitochondrial autophagy and protects against heart degeneration through regulating PGC-1α and decreasing troponin/ kinase contents. In addition, chrysin has an antioxidant effect and alleviates inflammatory mediators and AGEs contents, indicating its cardioprotective effect against D-gal-induced cardiac senescence. The study provides a new novel approach countering heart aging using chrysin that acts as Sirt/Nrf2 stimulant and AGE inhibitor modulating oxidative stress, mitochondrial biogenesis, autophagy, and necrosis