Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.
Cytokine
; 180: 156635, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38749277
ABSTRACT
BACKGROUND:
Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA.METHODS:
LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot.RESULTS:
Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization.CONCLUSION:
Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Transdução de Sinais
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Ratos Sprague-Dawley
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Fosfatidilinositol 3-Quinases
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Osteoartrite do Joelho
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Proteína HMGB1
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Proteínas Proto-Oncogênicas c-akt
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Receptor para Produtos Finais de Glicação Avançada
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Neuralgia
Limite:
Animals
Idioma:
En
Revista:
Cytokine
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article