Norisoboldine

Norisoboldine might be a potential therapeutic agent for rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses. Norisoboldine inhibits the macrophage activation and the resultant production of pro-inflammatory cytokines via down-regulating the activation of MAPKs signaling pathways rather than NF-κB.(In Vitro):Norisoboldine (1~30 μM; 0~24 hours; CD4+T cells) activates AhR under hypoxic microenvironment and significantly downregulates mRNA expression of miR-31.Norisoboldine (30 μM; 0~24 hours; CD4+T cells) inhibits glycolysis in hypoxia.Norisoboldine (1~30 μM; 0~72 hours; Treg cells) promotes Treg differentiation in hypoxia.Norisoboldine (10, 30 μM) facilitates the disassociation of HSP90/AhR complexes, the nuclear translocation of AhR, and the formation of AhR/ARNT complexes. Norisoboldine induces generation of Treg cells in hypoxia is independent of miR-31.(In Vivo):Norisoboldine (10~40 mg/kg; p.o.; 20 days) significantly reduces the severity of joint swelling and erythema during the course of the experiment.Norisoboldine (40 mg/kg; i.g.; 10 days) induces enhancement of CYP1A1 expression and suppresses expressions of Glut1 and HK2 in colons.