| Author | Opretzka, Luiza Carolina França | |
| Author | Espírito-Santo, Renan Fernandes do | |
| Author | Nascimento, Olívia Azevedo | |
| Author | Abreu, Lucas Silva | |
| Author | Alves, Iura Muniz | |
| Author | Döring, Eva | |
| Author | Soares, Milena Botelho Pereira | |
| Author | Velozo, Eudes da Silva | |
| Author | Laufer, Stefan A. | |
| Author | Villarreal, Cristiane Flora | |
| Access date | 2019-08-06T18:16:30Z | |
| Available date | 2019-08-06T18:16:30Z | |
| Document date | 2019 | |
| Citation | OPRETZKA, Luiza Carolina França et al. Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms. International Immunopharmacology, v. 72, p. 31–39, 2019. | pt_BR |
| ISSN | 1567-5769 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/34635 | |
| Sponsorship | Fundação de Amparo à Pesquisa do Estado da Bahia and the Conselho Nacional de Desenvolvimento Científico e Tecnológico. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Finance Code 01. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | Antinocicepção | pt_BR |
| Subject in Portuguese | Anti-inflamatória | pt_BR |
| Subject in Portuguese | Cromonas | pt_BR |
| Subject in Portuguese | NF-κB | pt_BR |
| Subject in Portuguese | Citocinas | pt_BR |
| Subject in Portuguese | Receptores glicocorticóides | pt_BR |
| Title | Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.intimp.2019.03.044 | |
| Abstract | Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5-20 μM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5-20 μM) reduced TNF-α, IL-6 and IL-1β production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1β, IL-6 and TNF-α). 3 (5-20 μM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Eberhard Karls Universität Tübingen. Institute of Pharmaceutical Sciences. Department of Pharmaceutical Chemistry. Tübingen, Germany. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Eberhard Karls Universität Tübingen. Institute of Pharmaceutical Sciences. Department of Pharmaceutical Chemistry. Tübingen, Germany. | pt_BR |
| Affilliation | Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Subject | Chromones | pt_BR |
| Subject | Anti-inflammatory | pt_BR |
| Subject | Antinociception | pt_BR |
| Subject | NF-κB | pt_BR |
| Subject | Cytokines | pt_BR |
| Subject | Glucocorticoid receptor | pt_BR |
