7-Hydroxycoumarin mitigates the severity of collagen-induced arthritis in rats by inhibiting proliferation and inducing apoptosis of fibroblast-like synoviocytes via suppression of Wnt/ß-catenin signaling pathway.
Phytomedicine
; 94: 153841, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34752968
ABSTRACT
BACKGROUND:
7-Hydroxycoumarin (7-HC) as a coumarin compound is widely found in Chinese herbs and exhibits diverse biological activities. Promoting cell apoptosis of fibroblast-like synoviocytes (FLS) is a meaningful strategy for rheumatoid arthritis (RA). Though the protective effect of 7-HC on RA experimental models has been reported, the specific mechanisms, especially the possible relationships of this effect to regulating FLS proliferation and apoptosis, still need clarification.PURPOSE:
This study clarified the therapeutic effects of 7-HC on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms.METHODS:
In vivo, 7-HC (15, 30 or 60 mg/kg) was intraperitoneally given to CIA rats, and its therapeutic effect and anti-inflammatory activity were evaluated. Ki67 immunohistochemistry, TUNEL assay and synovial proteins detection were conducted. In vitro, after treating with 7-HC (20, 40 or 80 µM) in TNF-α-stimulated RA FLS (MH7A cell line), cell proliferation and apoptosis were examined. The involvement of Wnt/ß-catenin pathway was checked in vivo and in vitro.RESULTS:
7-HC attenuated the severity of rat CIA, evidenced by the reduction of paw swelling, arthritis index, joint damage, collagen type II antibody serum level, and IL-1ß, IL-6, TNF-α production in serum and synovium. Particularly, 7-HC in vivo had anti-proliferative and pro-apoptotic effects on CIA rat synovial cells, indicated by reduced synovial Ki67 expression, raised synovial apoptosis index, decreased Bcl-2 protein level and increased level of Bax and cleaved caspase 3 protein. Further, 7-HC in vitro suppressed proliferation and promoted apoptosis of TNF-α-stimulated MH7A cells by regulating the mitochondrial pathway. Mechanistically, 7-HC treatment inhibited Wnt/ß-catenin pathway, suggested by the reduction of pathway-related proteins (e.g. Wnt1, LRP6, p-GSK-3ß (Ser9), ß-catenin, cyclin D1 and c-Myc), the recovery of GSK-3ß activity and the inhibition of ß-catenin nuclear translocation. As expected, combined use of lithium chloride, an activator of Wnt/ß-catenin signaling, reversed the anti-proliferative and pro-apoptotic effects of 7-HC in vitro.CONCLUSION:
7-HC relieved the severity of rat CIA by inhibiting cell proliferation and inducing apoptosis of rheumatoid FLS via inhibition of Wnt/ß-catenin pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Sinoviócitos
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2022
Tipo de documento:
Article