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<p>Myocardial ischemia-reperfusion injury (MIRI) represents a major clinical challenge in cardiovascular therapy. The NLRP3 inflammasome plays a critical role in the pathogenesis of MIRI, yet the effect of Acteoside (Act) on NLRP3 inflammasome during MIRI remains unclear. Network pharmacology combined with molecular docking was employed to predict and validate the key targets and pathways underlying Act-mediated regulation of MIRI-related pyroptosis. For the in vivo study, a rat MIRI model was established via 30&#xa0;min of left anterior descending coronary artery ligation followed by 2&#xa0;h of reperfusion. Rats were randomly divided into four groups: the Sham group, the MIRI model group, the Act pretreatment plus MIRI group, and the Act pretreatment plus MIRI plus LY294002 (a PI3K inhibitor) group. For the in vitro assay, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) and then treated with Act alone or in combination with LY294002. Cardiac function, myocardial infarct size, myocardial injury, histological alterations, and mitochondrial morphological changes were assessed. Oxidative stress, cardiomyocyte apoptosis, and the levels of inflammatory cytokines IL-1β and IL-18 were detected. The expression of NLRP3 inflammasome-related proteins and PI3K/Akt signaling pathway proteins were measured. Network pharmacology analysis identified the PI3K/Akt signaling pathway as a key mechanism mediating the effects of Act on MIRI. Molecular docking results confirmed that Act interacts with core components of the NLRP3 inflammasome, and that the NLRP3 inflammasome is associated with the PI3K/Akt pathway. Pretreatment with Act alleviated MIRI-induced myocardial injury, improved cardiac function and mitochondrial morphology, inhibited NLRP3 inflammasome activation, promoted the phosphorylation of PI3K/Akt, suppressed cardiomyocyte apoptosis and oxidative stress, and reduced the levels of IL-1β and IL-18. Notably, these protective effects of Act were partially reversed by LY294002. Act attenuates MIRI by inhibiting the NLRP3 inflammasome through activation of the PI3K/Akt signaling pathway, indicating its potential as a promising therapeutic agent for MIRI.</p>

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Acteoside attenuates myocardial ischemia reperfusion injury by inhibiting the NLRP3 inflammasome activity via the PI3K/Akt signaling pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Linlin Jia,
  • Hong Cao,
  • Yang Yang,
  • Yuxin Guo,
  • Zhiqiang Zhang,
  • Qiliang Sun,
  • Haibo Yu,
  • Xin Yang,
  • Dilip Dhakal,
  • Li Guo,
  • Guangyuan Yang

摘要

Myocardial ischemia-reperfusion injury (MIRI) represents a major clinical challenge in cardiovascular therapy. The NLRP3 inflammasome plays a critical role in the pathogenesis of MIRI, yet the effect of Acteoside (Act) on NLRP3 inflammasome during MIRI remains unclear. Network pharmacology combined with molecular docking was employed to predict and validate the key targets and pathways underlying Act-mediated regulation of MIRI-related pyroptosis. For the in vivo study, a rat MIRI model was established via 30 min of left anterior descending coronary artery ligation followed by 2 h of reperfusion. Rats were randomly divided into four groups: the Sham group, the MIRI model group, the Act pretreatment plus MIRI group, and the Act pretreatment plus MIRI plus LY294002 (a PI3K inhibitor) group. For the in vitro assay, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) and then treated with Act alone or in combination with LY294002. Cardiac function, myocardial infarct size, myocardial injury, histological alterations, and mitochondrial morphological changes were assessed. Oxidative stress, cardiomyocyte apoptosis, and the levels of inflammatory cytokines IL-1β and IL-18 were detected. The expression of NLRP3 inflammasome-related proteins and PI3K/Akt signaling pathway proteins were measured. Network pharmacology analysis identified the PI3K/Akt signaling pathway as a key mechanism mediating the effects of Act on MIRI. Molecular docking results confirmed that Act interacts with core components of the NLRP3 inflammasome, and that the NLRP3 inflammasome is associated with the PI3K/Akt pathway. Pretreatment with Act alleviated MIRI-induced myocardial injury, improved cardiac function and mitochondrial morphology, inhibited NLRP3 inflammasome activation, promoted the phosphorylation of PI3K/Akt, suppressed cardiomyocyte apoptosis and oxidative stress, and reduced the levels of IL-1β and IL-18. Notably, these protective effects of Act were partially reversed by LY294002. Act attenuates MIRI by inhibiting the NLRP3 inflammasome through activation of the PI3K/Akt signaling pathway, indicating its potential as a promising therapeutic agent for MIRI.