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<p>To investigate the effects of pterostilbene (PTB) and the cGAS-STING signaling pathway on inflammation and pyroptosis in myocardial ischemia-reperfusion injury (MIRI), and to elucidate their underlying regulatory relationship. A MIRI cell model was induced by oxygen-glucose deprivation/reperfusion (OGD/R). Cells were treated with PTB and/or the cGAS-STING signaling pathway inhibitor H151. The effects of PTB and cGAS on OGD/R-induced cardiomyocytes were assessed using CCK-8, ELISA, western blot, and immunofluorescence assays. An ex vivo MIRI model was established using tree shrews, which were administered PTB via perfusion. The effects of PTB on MIRI in tree shrews were evaluated by 2,3,5-Triphenyltetrazolium chloride staining, Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling staining, western blot, and enzyme-linked immunosorbent assay. OGD/R induction inhibited cardiomyocyte viability, promoted the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), increased the expression of pyroptosis-related proteins (NLRP3, GSDMD, cleaved GSDMD, caspase 1, and cleaved caspase 1), and activated the cGAS-STING signaling pathway. Treatment with PTB and H151 significantly alleviated OGD/R-induced injury in cardiomyocytes and in the myocardial tissue of tree shrews with MIRI, and suppressed the expression of inflammatory and pyroptosis-related factors. Furthermore, the combination of PTB and H151 enhanced the inhibitory effects of H151 on OGD/R-induced cellular inflammation and pyroptosis. Mechanistic studies indicated that PTB exerts its protective effects by inhibiting the activation of the cGAS-STING signaling pathway. PTB attenuates inflammation and pyroptosis in OGD/R-induced cardiomyocytes and in the myocardial tissue of tree shrews with MIRI by suppressing the cGAS-STING signaling pathway.</p>

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The role of pterostilbene in alleviating inflammatory response and pyroptosis in myocardial ischemia-reperfusion by inhibiting the cGAS-STING pathway

  • 期刊论文

  • 发表日期：

    2026年5月8日

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  • Hui Li,
  • Lingying Zhu,
  • Yongsheng He,
  • Dan Yan,
  • Jigang He

摘要

To investigate the effects of pterostilbene (PTB) and the cGAS-STING signaling pathway on inflammation and pyroptosis in myocardial ischemia-reperfusion injury (MIRI), and to elucidate their underlying regulatory relationship. A MIRI cell model was induced by oxygen-glucose deprivation/reperfusion (OGD/R). Cells were treated with PTB and/or the cGAS-STING signaling pathway inhibitor H151. The effects of PTB and cGAS on OGD/R-induced cardiomyocytes were assessed using CCK-8, ELISA, western blot, and immunofluorescence assays. An ex vivo MIRI model was established using tree shrews, which were administered PTB via perfusion. The effects of PTB on MIRI in tree shrews were evaluated by 2,3,5-Triphenyltetrazolium chloride staining, Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling staining, western blot, and enzyme-linked immunosorbent assay. OGD/R induction inhibited cardiomyocyte viability, promoted the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), increased the expression of pyroptosis-related proteins (NLRP3, GSDMD, cleaved GSDMD, caspase 1, and cleaved caspase 1), and activated the cGAS-STING signaling pathway. Treatment with PTB and H151 significantly alleviated OGD/R-induced injury in cardiomyocytes and in the myocardial tissue of tree shrews with MIRI, and suppressed the expression of inflammatory and pyroptosis-related factors. Furthermore, the combination of PTB and H151 enhanced the inhibitory effects of H151 on OGD/R-induced cellular inflammation and pyroptosis. Mechanistic studies indicated that PTB exerts its protective effects by inhibiting the activation of the cGAS-STING signaling pathway. PTB attenuates inflammation and pyroptosis in OGD/R-induced cardiomyocytes and in the myocardial tissue of tree shrews with MIRI by suppressing the cGAS-STING signaling pathway.