| Author | Costa, José Fernando Oliveira | |
| Author | Barbosa Filho, José Maria | |
| Author | Maia, Gabriela Lemos de Azevedo | |
| Author | Guimarães, Elisalva Teixeira | |
| Author | Meira, Cássio Santana | |
| Author | Santos, Ricardo Ribeiro dos | |
| Author | Pontes-de-Carvalho, Lain Carlos | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2014-10-31T12:28:26Z | |
| Available date | 2014-10-31T12:28:26Z | |
| Document date | 2014 | |
| Citation | COSTA, J. F. O. Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia. International Immunopharmacology, n. 14, S1567-5769, p. 00373-7, 2014. | pt_BR |
| ISSN | 1567-5769 | |
| URI | https://www.arca.fiocruz.br/handle/icict/8701 | |
| Language | eng | pt_BR |
| Publisher | Elsevier B.V | pt_BR |
| Rights | open access | pt_BR |
| Title | Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia | pt_BR |
| Type | Article | pt_BR |
| DOI | dx.doi.org/10.1016/j.intimp.2014.09.021 | |
| Abstract | Betulinic acid (BA) is a lupane-type triterpene with a number of biological activities already reported. While
potent anti-HIV and antitumoral activities were attributed to BA, it is considered to have a moderate antiinflammatory
activity. Here we evaluated the effects of BA in a mouse model of endotoxic shock. Endotoxemia
was induced through intraperitoneally LPS administration, nitric oxide (NO) and cytokines were assessed by
Griess method and ELISA, respectively. Treatment of BALB/c mice with BA at 67 mg/kg caused a 100% survival
against a lethal dose of lipopolysaccharide (LPS). BA treatment caused a reduction in TNF-α production induced
by LPS but did not alter IL-6 production. Moreover, BA treatment increased significantly the serumlevels of IL-10
compared to vehicle-treated, LPS-challenged mice. To investigate the role of IL-10 in BA-induced protection,
wild-type and IL-10−/− mice were studied. In contrast to the observations in IL-10+/+ mice, BA did not protect
IL-10−/− mice against a lethal LPS challenge. Addition of BA inhibited the production of pro-inflammatory
mediators by macrophages stimulated with LPS, while promoting a significant increase in IL-10 production.
BA-treated peritoneal exudate macrophages produced lower concentrations of TNF-α and NO and higher concentrations
of IL-10 upon LPS stimulation. Similarly, macrophages obtained from BA-treated mice produced
less pro-inflammatory mediators and increased IL-10 when compared to non-stimulated macrophages obtained
fromvehicle-treatedmice. In conclusion,we have shown that BA has a potent anti-inflammatory activity in vivo,
protecting mice against LPS by modulating TNF-α production by macrophages in vivo through a mechanism
dependent on IL-10. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil | pt_BR |
| Affilliation | Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil | pt_BR |
| Affilliation | Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / State University of Bahia. Department of Life Sciences. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil | pt_BR |
| Subject | Betulinic acid | pt_BR |
| Subject | Endotoxemia | pt_BR |
| Subject | Anti-inflammatory activity | pt_BR |
| Subject | Macrophages | pt_BR |
| Subject | Cytokines | pt_BR |
