Tangeretin Attenuates Cerebral Ischemia–Reperfusion-Induced Neuronal Pyroptosis by Inhibiting AIM2 Inflammasome Activation via Regulating NRF2
Pyroptosis is closely involved in the pathopoiesis of cerebral ischemia and reperfusion (I/R) injury which seriously dangers human’s life. Studies report that tangeretin (TANG), which is enriched in the peel of Citrus reticulata , has neuroprotective effects. Here, we explored whether absent in mela...
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Veröffentlicht in: | Inflammation 2024-02, Vol.47 (1), p.145-158 |
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Sprache: | eng |
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Zusammenfassung: | Pyroptosis is closely involved in the pathopoiesis of cerebral ischemia and reperfusion (I/R) injury which seriously dangers human’s life. Studies report that tangeretin (TANG), which is enriched in the peel of
Citrus reticulata
, has neuroprotective effects. Here, we explored whether absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis is involved in the cerebral I/R injury and the protective mechanism of TANG against cerebral I/R injury. In this study, we found that TANG treatment effectively alleviated I/R-induced brain injury and inhibited neuronal pyroptosis in an
in vivo
mice model with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and in an
in vitro
hippocampal HT22 cell model with oxygen–glucose deprivation and reoxygenation (OGD/R) injury. Furthermore, we found TANG inhibited cerebral I/R-induced neuronal AIM2 inflammasome activation
in vivo
and
in vitro
via regulating nuclear factor E2-related factor 2 (NRF2). Moreover, administration of ML385, a chemical inhibitor of NRF2, notably blocked the neuroprotective effects of TANG against cerebral I/R injury. In conclusion, TANG attenuates cerebral I/R-induced neuronal pyroptosis by inhibiting AIM2 inflammasome activation via regulating NRF2. These findings indicate TANG is a potential therapeutic agent for cerebral I/R injury. |
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ISSN: | 0360-3997 1573-2576 |
DOI: | 10.1007/s10753-023-01900-8 |