Asiaticoside alleviates myocardial ischemia-reperfusion injury in rats by inhibiting NLRP3 inflammasome-mediated pyroptosis

BIAN Fenlan; NI Shiyao; ZHAO Peng; QI Maonanxing; TANG Bi; WANG Hongju; KANG Pinfang; LIU Jinjun

doi:10.12122/j.issn.1673-4254.2025.05.10

Abstract：Objective To study the mechanism mediating the protective effect of asiaticoside(AS)against myocardial ischemia-reperfusion injury(MIRI)in rats.Methods Fifty SD rats were randomized into sham-operated group,MIRI model group and AS treatment group.AS treatment was administered at low,moderate and high doses by daily gavage for 2 weeks before MIRI modeling(n=10).Serum levels of lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),interleukin-18(IL-18)and IL-1β,the volume of myocardial infarction and ischemia,and myocardial pathologies of the rats were determined or observed.The protein expression levels of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18 in the myocardial tissues were detected using Western blotting.The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation(H/R)injury.Results The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18.AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner.In the H9C2 cell model of H/R injury,AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18.Molecular docking studies showed that AS had a strong binding affinity with NLRP3.Conclusion Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.