The Natural Compound Notopterol Binds and Targets JAK2/3 to Ameliorate Inflammation and Arthritis.
Cell Rep
; 32(11): 108158, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32937124
ABSTRACT
The traditional Chinese medicinal herb Notopterygium incisum Ting ex H.T. Chang has anti-rheumatism activity, and a mass spectrometry assay of patients' serum after administration of the herb revealed that notopterol is the most abundant component enriched. However, the functions of notopterol and its molecular target in rheumatoid arthritis (RA) treatment remain unknown. Here, we show in different RA mouse strains that both oral and intraperitoneal administration of notopterol result in significant therapeutic effects. Mechanistically, notopterol directly binds Janus kinase (JAK)2 and JAK3 kinase domains to inhibit JAK/signal transducers and activators of transcription (JAK-STAT) activation, leading to reduced production of inflammatory cytokines and chemokines. Critically, combination therapy using both notopterol and tumor necrosis factor (TNF) blocker results in enhanced therapeutic effects compared to using TNF blocker alone. We demonstrate that notopterol ameliorates RA pathology by targeting JAK-STAT signaling, raising the possibility that notopterol could be effective in treating other diseases characterized by aberrant JAK-STAT signaling pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
Problema de salud:
1_doencas_nao_transmissiveis
Asunto principal:
Artritis Reumatoide
/
Cumarinas
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Janus Quinasa 2
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Janus Quinasa 3
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Inflamación
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article