2. Academic Validation
  3. The Natural Compound Notopterol Binds and Targets JAK2/3 to Ameliorate Inflammation and Arthritis

The Natural Compound Notopterol Binds and Targets JAK2/3 to Ameliorate Inflammation and Arthritis

  • Cell Rep. 2020 Sep 15;32(11):108158. doi: 10.1016/j.celrep.2020.108158.
Qiong Wang 1,  Xin Zhou 2,  Long Yang 3,  Yongjian Zhao 4,  Zhihuan Chew 5,  Jun Xiao 5,  Chang Liu 2,  Xin Zheng 5,  Yuxiao Zheng 5,  Qi Shi 4,  Qianqian Liang 6,  Yongjun Wang 7,  Hongyan Wang 8
Affiliations

Affiliations

  • 1 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 2 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Cancer Center, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.
  • 3 Department of Rehabilitation Medicine, Shanghai Eighth People's Hospital, Shanghai 200235, China.
  • 4 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
  • 5 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
  • 6 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: liangqianqiantcm@126.com.
  • 7 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: yjwang8888@126.com.
  • 8 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China. Electronic address: hongyanwang@sibcb.ac.cn.
PMID: 32937124 DOI: 10.1016/j.celrep.2020.108158
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.

Keywords

Collagen Induced Arthritis; LPS/IFNγ; Traditional Chinese Medicine; compound; macrophage.

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