Antiinflammatory effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on zymosan-induced arthritis in mice

Abstract

We investigated the antiinflammatory properties of a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet. Zymosan-induced arthritis and pleurisy in Swiss and C57/Bl6 mice (n = 10 per group). Western blot analysis was performed to analyze nuclear factor-kappaB (NFkappaB) translocation in mice peritoneal macrophages stimulated in vitro with zymosan (500 microg/ml). ELISA was performed to evaluate cytokine levels in knee joints. Values of p </= 0.05 were regarded as significant. Zymosan intra-articular (i. a.) injection (500microg/ cavity) induced a significant increase in knee joint diameter within 6 h, peaked within 24 h and remained above control values for 20 days. Orally-given (p. o.) TNTP (100-200 mg/ kg) inhibited zymosan-induced increase in knee joint diameter and protein extravazation into synovial cavity within 6 h. TNTP (100-200 mg/kg, p. o.) also inhibited total leukocyte influx into the synovial space and tissue, as well as into the mice pleural cavity, due to neutrophil impairment 6 h after zymosan stimulation. The increase in TNF-alpha, IL-1beta and CXCL8/IL-8 levels that were detected in knee synovial extracts obtained from zymosan-stimulated mice was also inhibited by TNTP (100 mg/kg, p. o.). Moreover, the incubation of mice peritoneal macrophages with TNTP (100 mug/ml) inhibited zymosan (500 microg/ml)-induced NFkappaB translocation into the nucleus 6 h after stimulation. Taken together, these results indicate that TNTP present an important antiinflammatory effect, inhibiting zymosan-induced arthritis in mice via the impairment of TNF-alpha, IL-1beta and CXCL8/IL-8 generation, as well as NFkappaB signaling pathway.