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Orientin inhibits inflammation in chondrocytes and attenuates osteoarthritis through Nrf2/NF-κB and SIRT6/NF-κB pathway.
- Source :
-
Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2023 Nov; Vol. 41 (11), pp. 2405-2417. Date of Electronic Publication: 2023 May 08. - Publication Year :
- 2023
-
Abstract
- Effects of Orientin on murine chondrocytes treated with interleukin-1β (IL-1β) were evaluated using qPCR, western blot analysis, ELISA, and immunofluorescent staining in vitro. In vivo, We established a standard OA model by performing the destabilized medial meniscus (DMM) surgery on C57BL/6 mice, and assessed healing effect of Orientin by X-ray imaging, histopathological analysis, immunohistochemical staining. Osteoarthritis (OA) is the most common form of degenerative joint disease in clinic and the chondrocyte inflammation plays the most important role in OA development. The natural flavonoid compound (Orientin) has anti-inflammatory bioactive properties in the treatment of various diseases. But studies have not explored whether Orientin modulates OA progression. In this study, a significant suppression in IL-1β-mediated pro-inflammatory mediators and the degradation of cartilage extracellular matrix (ECM) was observed in vitro through qPCR, western blot analysis, ELISA, and immunofluorescent staining after the treatment with Orientin. In addition, Orientin abrogated DMM surgery induced cartilage degradation in mice, which was assessed by X-ray imaging, histopathological analysis, immunohistochemical staining. Mechanistic studies showed that Orientin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and SIRT6 signaling pathway. These results provide evidence that Orientin serves as a potentially viable compound for the treatment of OA.<br /> (© 2023 Orthopaedic Research Society.)
- Subjects :
- Mice
Animals
Chondrocytes metabolism
NF-kappa B metabolism
NF-E2-Related Factor 2 metabolism
NF-E2-Related Factor 2 pharmacology
Mice, Inbred C57BL
Inflammation drug therapy
Inflammation metabolism
Flavonoids pharmacology
Flavonoids therapeutic use
Menisci, Tibial pathology
Interleukin-1beta metabolism
Cells, Cultured
Osteoarthritis metabolism
Sirtuins metabolism
Sirtuins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1554-527X
- Volume :
- 41
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of orthopaedic research : official publication of the Orthopaedic Research Society
- Publication Type :
- Academic Journal
- Accession number :
- 37186383
- Full Text :
- https://doi.org/10.1002/jor.25573