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.

中药Not活Ting ex HT Chang具有抗风湿作用，服用草药后对患者血清进行的质谱分析显示，诺丹酚是最丰富的成分。然而，在人体类风湿关节炎（RA）治疗中，诺托泊尔及其分子靶标的功能尚不清楚。在这里，我们显示了在不同的RA小鼠品系中，诺美特尔的口服和腹膜内给药均可产生显着的治疗效果。从机制上讲，新蝶呤直接结合Janus激酶（JAK）2和JAK3激酶域，以抑制JAK /信号转导子和转录激活子（JAK-STAT）激活，从而导致炎性细胞因子和趋化因子的产生减少。至关重要的是 与单独使用TNF阻滞剂相比，同时使用诺丹酚和肿瘤坏死因子（TNF）阻滞剂的联合治疗可提高治疗效果。我们证明，诺托普尔通过靶向JAK-STAT信号改善了RA病理，提高了诺托诺尔可以有效治疗以异常JAK-STAT信号通路为特征的其他疾病的可能性。