Antiinflammatory effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on zymosan-induced arthritis in mice.
OBJECTIVE
We investigated the antiinflammatory properties of a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Penido
C
C
Departamento de Farmacologia Aplicada, Far-Manguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, 21041-250, Rio de Janeiro, RJ, Brazil.
Conte
F P
FP
Chagas
M S S
MS
Rodrigues
C A B
CA
Pereira
J F G
JF
Henriques
M G M O
MG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D036701:Limonins / Q000494:pharmacology*; D017737:Macrophages, Peritoneal; D008297:Male; D029582:Meliaceae; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy / Q000379:methods; D028321:Plant Preparations / Q000494:pharmacology*; D012639:Seeds; D050863:Synaptotagmin I / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D015054:Zymosan
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D036701:Limonins; D016328:NF-kappa B; D028321:Plant Preparations; D050863:Synaptotagmin I; D015054:Zymosan