Withaferin A alleviates inflammation in animal models of arthritis by inhibiting the NF-κB pathway and cytokine release.
Chem Biol Interact
; 398: 111114, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38897341
ABSTRACT
Withaferin A, a steroid lactone from Withania somnifera, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties. This study investigated the effects of withaferin A on collagen-induced arthritis (CIA) rats, focusing on NF-κB p65 regulation and cytokine release. Withaferin A (50 mg/kg b.wt., orally) or methotrexate (0.25 mg/kg b.wt., i.p., as a reference drug) was given to CIA rats daily for 20 days postarthritis induction. Joints were removed from nonarthritic and arthritic rats to assess the levels of NO, MPO, interleukin (IL)-1ß, IL-6, IL-10, TNF-α, COX-2, and NF-κB via ELISA. Furthermore, the mRNA expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB was also assessed through qPCR. Treatment with withaferin A significantly inhibited the levels of inflammatory cytokines and the transcription factor NF-κB; suppressed the expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB in the joint tissue of CIA rats; and reduced cartilage and bone destruction, as shown by H&E staining. To confirm the results obtained from biochemical and molecular studies and to determine the molecular target of withaferin A, we performed a molecular simulation of the potential targets of withaferin A, which identified the NF-κB pathway as its target. These results suggested that withaferin A effectively attenuated rheumatoid arthritis progression by inhibiting the activation of the NF-κB pathway and the downstream secretion of inflammatory cytokines.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
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Transdução de Sinais
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Citocinas
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NF-kappa B
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Vitanolídeos
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
2024
Tipo de documento:
Article