Notoginsenoside R1 Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Apoptosis via Activating Wnt/β-Catenin Signaling

Notoginsenoside R1 (NGR1), a natural triterpenoid saponin, is extracted from Panax notoginseng, and has cardiovascular and cerebrovascular protective effects due to anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Previous research has suggested a protective role for NGR1 in myocardial ischemia/reperfusion (MI/R) injury. However, the potential mechanisms involved have not been fully elucidated. Thus, the objective of our study was to validate the protective role of NGR1 in MI/R injury and to investigate its underlying mechanisms. Results showed that, in mice, NGR1 substantially improved heart function, reduced infarct area, and inhibited cardiomyocyte apoptosis. Mechanistically, network pharmacological predictions suggested that NGR1 could inhibit apoptosis by activating the Wnt signaling pathway. Experimentally, the protective effects of NGR1 in inhibiting cardiomyocyte apoptosis, improving cardiac function, and reducing infarct size were significantly attenuated with the use of the Wnt signaling inhibitor XAV-939. Collectively, our investigation demonstrated that NGR1 improves myocardial injury triggered by ischemia/reperfusion (I/R) by enhancing Wnt/[Formula: see text]-catenin pathway activity, which in turn suppresses apoptosis.