Total saponins of Aralia elata (Miq.) Seem. alleviate myocardial ischemia‐reperfusion injury by promoting NLRP3‐inflammasome inactivation via PI3K/Akt signaling

Abstract Total saponins of Aralia elata (Miq.) Seem. (TSAE) have been shown to play a significant role in cardiovascular protection, anti‐tumor, liver protection, anti‐oxidant stress, and anti‐inflammation. However, the specific mechanisms of TSAE in myocardial ischemia‐reperfusion injury (MIRI) remain largely elusive. Hearts from male Wistar rats were used to establish the isolated heart MIRI model. Using a multichannel physiological recorder, the whole course heart rate (HR), left ventricular development pressure (LVDP), and maximum rise/decrease rate of left ventricular pressure (±dp/dtmax) were recorded. 2,3,5‐triphenyl‐2H‐tetrazolium chloride staining observed the infarct area, while hematoxylin & eosin staining detected pathological changes in myocardial tissue. Creatine kinase, lactate dehydrogenase, total superoxide dismutase, and malondialdehyde concentrations were determined by enzyme‐linked immunosorbent assay. Immunohistochemistry, quantitative PCR, and western blot assay were used to assess the amounts of IL‐18 and IL‐1β, NLR family protein (NLRP3) inflammasome‐ and apoptosis‐related proteins, respectively. Treatment with TSAE or MCC950 (NLRP3‐specific inhibitor) significantly reduced the myocardial infarction area, alleviated pathological changes in myocardial tissues, enhanced LVDP and ±dp/dtmax levels, prevented myocardial oxidative damage, and inhibited NLRP3 inflammasome formation. In addition, TSAE enhanced Akt and GSK3β phosphorylation, and LY29004 co‐reperfusion markedly diminished the protective role of TSAE reperfusion on cardiac function, oxidative damage, and inflammatory responses. Collectively, TSAE treatment exhibited a protective effect on I/R‐triggered inflammatory responses, cell necrosis, and oxidative stress injury by stimulating PI3K/Akt signaling‐mediated NLRP3 inflammasome inhibition.