A standardized notoginseng extract exerts cardioprotection by attenuating apoptosis under endoplasmic reticulum stress conditions

• RGSE attenuated acute myocardial infarction-induced heart injury.
• RGSE inhibited oxidative stress and apoptosis during AMI in vivo and in vitro.
• TXNIP-NLRP3-IL-1β signaling, for the first time, was revealed to be activated in AMI, promoting cell death in the end.
• RGSE exerted cardioprotection by suppression of TXNIP/NLRP3 activation during ER stress.
• Ginsenosides Rh4, Rg5, Rk3, and Rk1 were the most abundant, and notoginsenoside T5/isomer was first identified in steamed notoginseng.

Panax notoginseng possesses therapeutic potential for cardiovascular disorders. Endoplasmic reticulum (ER) stress plays a critical role in cardiovascular disease. Here we show that a rare ginsenoside-standardized extract (RGSE) from notoginseng exerts cardioprotection via attenuating ER stress-associated apoptosis. A total of 18 ginsenosides with a concentration of 816.75 mg/g were characterized and quantified in RGSE. Ginsenoside Rh4, Rg5, Rk3, and Rk1 were the most abundant. RGSE at 50 and 100 mg/kg significantly attenuated myocardial infarction and improved cardiac function in acute myocardial infarction (AMI). RGSE also prevented myocardial ischemia-induced oxidative stress and apoptosis in vivo and in vitro. In addition, RGSE decreased the overexpression of GRP78, GRP94 and CHOP, and inhibited the phosphorylation of PERK and IRE1α in ER stress. Further investigation revealed that RGSE effectually inactivated TXNIP/NLRP3 signaling pathway in AMI hearts. These observations suggest a novel role for notoginseng in regulating AMI.