Débora Barbosa Vendramini-Costa1, Humberto Moreira Spindola2, Glaucia Coelho de Mello3, Edson Antunes3, Ronaldo Aloise Pilli4, João Ernesto de Carvalho5. 1. University of Campinas, Department of Organic Chemistry, Institute of Chemistry, Rua Josué de Castro s/n, Cidade Universitária Zeferino Vaz, CP 6154, Campinas, São Paulo 13081-970, Brazil; University of Campinas, Chemical, Biological and Agricultural Pluridisciplinary Research Center, CPQBA, Rua Alexandre Cazelatto, 999, Vila Betel, Paulínia, São Paulo 13148-218, Brazil. Electronic address: vendramini.debora@gmail.com. 2. University of Campinas, Chemical, Biological and Agricultural Pluridisciplinary Research Center, CPQBA, Rua Alexandre Cazelatto, 999, Vila Betel, Paulínia, São Paulo 13148-218, Brazil. 3. University of Campinas, Cidade Universitária Zeferino Vaz, Department of Pharmacology, Faculty of Medical Sciences, Campinas, São Paulo 13081-970, Brazil. 4. University of Campinas, Department of Organic Chemistry, Institute of Chemistry, Rua Josué de Castro s/n, Cidade Universitária Zeferino Vaz, CP 6154, Campinas, São Paulo 13081-970, Brazil. 5. University of Campinas, Chemical, Biological and Agricultural Pluridisciplinary Research Center, CPQBA, Rua Alexandre Cazelatto, 999, Vila Betel, Paulínia, São Paulo 13148-218, Brazil; University of Campinas, Cidade Universitária Zeferino Vaz, Faculty of Pharmaceutical Sciences, Campinas, São Paulo 13081-970, Brazil.
Abstract
AIMS: The present study aimed to further investigate the anti-inflammatory activity of goniothalamin (GTN), a styryl lactone, as well as its antinociceptive effects. MAIN METHODS: The anti-inflammatory activity was evaluated in models of paw edema induced by different mediators in mice and carrageenan-induced peritonitis. Evaluation of the antinociceptive effect was performed through acetic acid-induced writhing test and formalin test. Activity of GTN on gene expression levels of interleukin-1beta (IL-1β), induced nitric oxidase synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated in vitro in lipopolysaccharide (LPS)-stimulated macrophage (RAW 264.7), as well as gene expression and protein levels of tumor necrosis factor-alpha (TNF-α). KEY FINDINGS: Pretreatment with GTN (300 mg/kg) significantly reduced paw edema induced by compound 48/80, prostaglandin E2, phospholipase A2 and bradykinin. GTN (10, 30 and 100mg/kg) inhibited leukocyte migration in the peritonitis model and gene expression levels of IL-1β, iNOS and TNF-α, as well as TNF-α protein levels, in LPS-stimulated macrophages, without affecting COX-2 gene expression levels. GTN inhibited nociception induced by acetic acid in the writhing model and in the formalin test, when both neurogenic and inflammatory phases were inhibited. SIGNIFICANCE: For the first time the acute anti-inflammatory profile of GTN is characterized and its antinociceptive activity reported. The current study shows that GTN inhibits both vascular and cellular phases of inflammation, with bradykinin and PLA2 induced inflammation being the most affected by GTN. Its anti-inflammatory effects also involved the in vitro inhibition of gene expression of alarm cytokines and mediators as IL-1β, iNOS and TNF-α.
AIMS: The present study aimed to further investigate the anti-inflammatory activity of goniothalamin (GTN), a styryl lactone, as well as its antinociceptive effects. MAIN METHODS: The anti-inflammatory activity was evaluated in models of paw edema induced by different mediators in mice and carrageenan-induced peritonitis. Evaluation of the antinociceptive effect was performed through acetic acid-induced writhing test and formalin test. Activity of GTN on gene expression levels of interleukin-1beta (IL-1β), induced nitric oxidase synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated in vitro in lipopolysaccharide (LPS)-stimulated macrophage (RAW 264.7), as well as gene expression and protein levels of tumor necrosis factor-alpha (TNF-α). KEY FINDINGS: Pretreatment with GTN (300 mg/kg) significantly reduced paw edema induced by compound 48/80, prostaglandin E2, phospholipase A2 and bradykinin. GTN (10, 30 and 100mg/kg) inhibited leukocyte migration in the peritonitis model and gene expression levels of IL-1β, iNOS and TNF-α, as well as TNF-α protein levels, in LPS-stimulated macrophages, without affecting COX-2 gene expression levels. GTN inhibited nociception induced by acetic acid in the writhing model and in the formalin test, when both neurogenic and inflammatory phases were inhibited. SIGNIFICANCE: For the first time the acute anti-inflammatory profile of GTN is characterized and its antinociceptive activity reported. The current study shows that GTN inhibits both vascular and cellular phases of inflammation, with bradykinin and PLA2 induced inflammation being the most affected by GTN. Its anti-inflammatory effects also involved the in vitro inhibition of gene expression of alarm cytokines and mediators as IL-1β, iNOS and TNF-α.
Authors: Débora Barbosa Vendramini-Costa; Ralph Francescone; David Posocco; Vivianty Hou; Oxana Dmitrieva; Harvey Hensley; João Ernesto de Carvalho; Ronaldo Aloise Pilli; Sergei I Grivennikov Journal: Carcinogenesis Date: 2016-10-24 Impact factor: 4.944
Authors: Ismael Raitz; Roberto Y de Souza Filho; Lorena P de Andrade; Jose R Correa; Brenno A D Neto; Ronaldo A Pilli Journal: ACS Omega Date: 2017-07-20