Notoginsenoside R1 treatment facilitated Nrf2 nuclear translocation to suppress ferroptosis via Keap1/Nrf2 signaling pathway to alleviated high-altitude myocardial injury.

High-altitude myocardial injury (HAMI) represents a critical form of altitude illness for which effective drug therapies are generally lacking. Notoginsenoside R1, a prominent constituent derived from Panax notoginseng, has demonstrated various cardioprotective properties in models of myocardial ischemia/reperfusion injury, sepsis-induced cardiomyopathy, cardiac fibrosis, and myocardial injury. The potential utility of notoginsenoside R1 in the management of HAMI warrants prompt investigation. Following the successful construction of a HAMI model, a series of experimental analyses were conducted to assess the effects of notoginsenoside R1 at dosages of 50 mg/Kg and 100 mg/Kg. The results indicated that notoginsenoside R1 exhibited protective effects against hypoxic injury by reducing levels of CK, CK-MB, LDH, and BNP, leading to improved cardiac function and decreased incidence of arrhythmias. Furthermore, notoginsenoside R1 was found to enhance Nrf2 nuclear translocation, subsequently regulating the SLC7A11/GPX4/HO-1 pathway and iron metabolism to mitigate ferroptosis, thereby mitigating cardiac inflammation and oxidative stress induced by high-altitude conditions. In addition, the application of ML385 has confirmed the involvement of Nrf2 nuclear translocation in the therapeutic approach to HAMI. Collectively, the advantageous impacts of notoginsenoside R1 on HAMI have been linked to the suppression of ferroptosis via Nrf2 nuclear translocation signaling. [Display omitted] • High-altitude exposure can cause myocardial injury, signs of tissue hypoxia, and ECG abnormalities. • Notoginsenoside R1 ameliorated myocardial injury caused by high-altitude stimulation. • Notoginsenoside R1 decreased ferroptosis in myocardial cells. • The effects of notoginsenoside R1 were mediated through the Keap1/Nrf2 signaling pathway to facilitated Nrf2 nuclear translocation. [ABSTRACT FROM AUTHOR]