title: Pharmacological Properties of Riparin IV in Models of Pain and Inflammation.
abstract: Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56-100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED50values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56-25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund's adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production.
authors.affiliation: Faculdade de Farmácia, Universidade Federal da Bahia, 40170-290 Salvador, BA, Brazil. olivia_azevedo@hotmail.com.
authors.forename: Olívia Azevêdo
authors.initials: OA
authors.lastname: Nascimento
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, BA, Brazil. r.fernandes88@hotmail.com.
authors.forename: Renan Fernandes do
authors.initials: RF
authors.lastname: Espírito-Santo
authors.affiliation: Faculdade de Farmácia, Universidade Federal da Bahia, 40170-290 Salvador, BA, Brazil. luizacfo@ufba.br.
authors.forename: Luíza Carolina França
authors.initials: LC
authors.lastname: Opretzka
authors.affiliation: Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, 58051-900 João Pessoa, PB, Brazil. barbosa.ufpb@gmail.com.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Departamento de Bioquímica e Farmacologia, Universidade Federal do Piauí, 64049-550 Teresina, PI, Brazil. stanleychavez@ufpi.edu.br.
authors.forename: Stanley Juan Chavez
authors.initials: SJ
authors.lastname: Gutierrez
authors.affiliation: Faculdade de Farmácia, Universidade Federal da Bahia, 40170-290 Salvador, BA, Brazil. cfv@ufba.br.|Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, BA, Brazil. cfv@ufba.br.
authors.forename: Cristiane Flora
authors.initials: CF
authors.lastname: Villarreal
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, BA, Brazil. milena@bahia.fiocruz.br.|Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, 41253-190 Salvador, BA, Brazil. milena@bahia.fiocruz.br.
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005620:Freund's Adjuvant / Q000009:adverse effects; D015870:Gene Expression; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D059408:Pain Management; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001549:Benzamides; C556062:IL10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005620:Freund's Adjuvant; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: PGE2; anti-inflammatory; antinociception; cytokines; riparins