Gastrodin against oxidative stress-inflammation crosstalk via inhibiting mtDNA/TLR9 and JAK2/STAT3 signaling to ameliorate ischemic stroke injury.
Int Immunopharmacol
; 141: 113012, 2024 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-39182268
ABSTRACT
The pathway of Janus-activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) (termed as JAK2/STAT3) plays an active role in stroke-related inflammation induced by ischemic stress. Gastrodin, the primary compound in Gastrodia elata Bl, has been identified for its notable neuroprotective effects and demonstrated to ameliorate cerebral ischemia-reperfusion but its exact mechanisms governing this defense are still unclear. This study aims to investigate whether gastrodin can regulate mitochondrial function via the JAK2/STAT3 pathway to limit cerebral ischemia-reperfusion. In vivo, gastrodin significantly reduced infarct volume, improved neurobiological function, attenuated neuronal apoptosis, oxidative stress, mitochondrial impairment, mtDNA leakage, and inflammatory responses. At the cellular level, gastrodin administration rescued OGD/R-induced cell apoptosis, oxidative stress, and mitochondrial dysfunction. Mechanistically, gastrodin notably suppressed Toll-like receptor 9 (TLR9) expression, important for the recognition of disrupted endogenous DNA to produce inflammatory reactions. Furthermore, gastrodin mitigated inflammation by inhibiting JAK2/STAT3 signaling, influencing inflammatory factors to aggravate inflammation. Notably, the effects of gastrodin were abolished by Coumermycin A1 (C-A1), a JAK2 agonist, validating the role of JAK2/STAT3 signaling. In summary, gastrodin enhances the protective effect against mitochondrial damage in ischemic stroke by inhibiting JAK2/STAT3 signaling. Gastrodin is a possible therapy for cerebral ischemia.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Alcoholes Bencílicos
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ADN Mitocondrial
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Transducción de Señal
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Estrés Oxidativo
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Fármacos Neuroprotectores
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Factor de Transcripción STAT3
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Receptor Toll-Like 9
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Janus Quinasa 2
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Accidente Cerebrovascular Isquémico
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Glucósidos
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article