Diabetic cardiomyopathy (DCM) leads to
heart failure and death in diabetic patients, no effective treatment is available.
Notoginsenoside R1 (NGR1) is a novel
saponin that is derived from Panax notoginseng and our previous studies have showed cardioprotective and
neuroprotective effects of NGR1. However, its role in protecting against DCM remains unexplored. Herein, we examine potential effects of NGR1 on cardiac function of diabetic db/db mice and H9c2 cardiomyocytes treated by
advanced glycation end products (AGEs). In vitro experiments revealed that pretreatment with NGR1 significantly decreased AGEs-induced mitochondria injury, limited an increase in ROS, and reduced apoptosis in H9c2 cells. NGR1 eliminated ROS by promoting
estrogen receptor α expression, which subsequently activated Akt and Nrf2-mediated
anti-oxidant enzymes. In vivo investigation demonstrated that NGR1 significantly reduced serum
lipid levels,
insulin resistance, the expression of
enzymes related to
cardiomyopathy, and the expression of apoptotic
proteins. Finally, NGR1 improved cardiac dysfunction and attenuated histological abnormalities, as evidenced by elevating ejection fraction and fractional shortening, and reducing cardiac
fibrosis. Mechanistically, NGR1 promoted ERα expression, which led to the activation of Akt-Nrf2 signaling and the inhibition of the TGFβ pathway. Collectively, these results strongly indicate that NGR1 exerts cardioprotective effects against DCM through its inhibition of oxidative stress and apoptosis, and eventually suppresses cardiac
fibrosis and
hypertrophy, which suggests that NGR1 is a potential therapeutic medicine for the treatment of DCM.