title: Effect of gedunin on acute articular inflammation and hypernociception in mice.
abstract: Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005-5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB4, PGE2, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations.
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. fernando.conte@bio.fiocruz.br.
authors: Fernando P
authors: FP
authors: Conte
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. fausto.ferraris@incqs.fiocruz.br.
authors: Fausto K
authors: FK
authors: Ferraris
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. thadeucosta@far.fiocruz.br.
authors: Thadeu E M M
authors: TE
authors: Costa
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. patricia.pacheco.silva@gmail.com.
authors: Patricia
authors: P
authors: Pacheco
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. leonardoseito@far.fiocruz.br.
authors: Leonardo N
authors: LN
authors: Seito
authors: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Brazil. fdqcunha@fmrp.usp.br.|Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil. fdqcunha@fmrp.usp.br.
authors: Waldiceu A
authors: WA
authors: Verri
authors: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil. fdqcunha@fmrp.usp.br.
authors: Fernando Q
authors: FQ
authors: Cunha
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. cpenido@cdts.fiocruz.br.|Centro de Desenvolvimento Tecnológico em Saúde, CDTS/INCT-IDN, Fundação Oswaldo Cruz, Rio de Janeiro 21045-360, Brazil. cpenido@cdts.fiocruz.br.
authors: Carmen
authors: C
authors: Penido
authors: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil. gracahenriques@fiocruz.br.|Centro de Desenvolvimento Tecnológico em Saúde, CDTS/INCT-IDN, Fundação Oswaldo Cruz, Rio de Janeiro 21045-360, Brazil. gracahenriques@fiocruz.br.
authors: Maria G
authors: MG
authors: Henriques
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002470:Cell Survival; D019332:Endothelin-1 / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D036701:Limonins / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D059225:Nociception / Q000187:drug effects*; D010007:Osteochondritis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019332:Endothelin-1; D018836:Inflammation Mediators; D036701:Limonins; C106014:gedunin
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