Esculin Alleviates Osteoarthritis Progression Through the Sirt1/NF-κB Pathway.
Esculin
NF‐κB
Sirt1
inflammation
osteoarthritis
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
revised:
13
01
2024
received:
28
08
2023
accepted:
23
01
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
1
10
2024
Statut:
aheadofprint
Résumé
Osteoarthritis (OA), a joint disease associated with inflammatory processes, contributes to joint destruction. Esculin (ESC) extracted from the stem bark of Fraxinus rhynchophylla Hance has been shown to possess anti-inflammatory properties. In this study, we investigated the effect of ESC on chondrocytes treated with IL-1β and its molecular mechanism. The importance and potential mechanism of ESC in the progression of OA were evaluated. The viability of chondrocytes after exposure to ESC was examined through the CCK-8 assays. The cells were then subjected to quantitative polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA) techniques to analyze the degradation of the extracellular matrix (ECM) and occurrence of inflammation. The NF-κB mechanism was evaluated by western blot analysis, immunofluorescence (IF), and luciferase reporter assay. Molecular docking was performed to allow for predictions on proteins that interact with ESC. Moreover, the significance of Sirt1 was explored through a knockdown experiment based on siRNA. Micro-computed tomography (CT), H&E, Safranin O-Fast Green (S-O), and immunohistochemical analyses were carried out to assess the treatment efficacy of ESC on OA in destabilization of medial meniscus (DMM) models. ESC treatment effectively inhibited ECM degradation, modulated the levels of pro-inflammatory factors, and regulated the NF-κB signaling in chondrocytes exposed to IL-1β. Mechanistically, we found that ESCs bound to Sirt1 to inhibit the activity of the NF-κB mechanism. Furthermore, ESC treatment suppressed OA progression in the DMM models. Our findings reveal that ESC ameliorates OA progression via modulating the Sirt1/NF-κB axis. This demonstrates that ESC has the potential to be applied in the treatment of OA.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Zhejiang Provincial Medical and Health Science and Technology Plan
ID : 2022KY1430
Informations de copyright
© 2024 John Wiley & Sons Ltd.
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