期刊
CELL REPORTS
卷 32, 期 11, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.108158
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资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
- National Natural Science Foundation [81930038, 81825011, 81822050, 81920108032]
- Leading Medical Talents in Shanghai [2019LJ02]
- Dawn Plan of Shanghai Municipal Education Commission [19SG39]
- Program for Innovative Research Team of Ministry of Science and Technology of China [2015RA4002]
- Innovation Team'' development projects [IRT1270]
- Shanghai TCM Medical Center of Chronic Disease [2017ZZ01010]
- Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan [ZY(2018-2020)-CCCX-3003]
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.
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