Coompo Research Chemicals

After boosted on day 21, mice were treated with norisoboldine (10, 20, 40 mg/kg) for twenty consecutive days. The clinical scores, body weight changes and joint histopathology were evaluated. Norisoboldine treatment significantly alleviated the severity of the disease, based on the reduced clinical scores and elevated the lowered body weights of model mice. Meanwhile, this alkaloid dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and protected joint from destruction. Additionally, the serum level of anti-CII IgG and the CII-stimulated lymphocyte proliferation were remarkably decreased in the groups administered with norisoboldine. An assessment of Th1 function using the delayed-type hypersensitivity model confirmed that norisoboldine also significantly suppressed the enhanced T cell responses in vivo. These findings suggest that 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.

It has been previously implicated to be able to ameliorate the synovial inflammation and abnormal immune conditions in collagen-induced arthritis of mice. To get insight to the potential anti-inflammatory mechanisms of this alkaloid compound, the present study was undertaken to explore the effects of norisoboldine on the production of pro-inflammatory cytokines from macrophages stimulated by lipopolysaccharide. In vitro, norisoboldine substantially reduced the production of nitric oxide (NO), tumor necrosis factor (TNF)-α as well as interleukin (IL)-1β from RAW264.7 macrophage cells in a concentration-dependent manner, whereas it only slightly reduced the production of interleukin-6 (IL-6) at both protein and transcription levels. Of note, the preventive effects of norisoboldine on the release of pro-inflammatory cytokines were correlated with the inhibitory action on the phosphorylations of mitogen-activated protein (MAP) kinases including p38, extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), but not on the activation and translocation of nuclear factor-κB (NF-κB). It can be therefore concluded that 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.