In vivo and in vitro activity of isolated compounds from Brazilian propolis on the modulation of the inflammatory process

Author(s)

Marcelo Franchin

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2016-02-25

Examining board members

Pedro Luiz Rosalen; Severino Matias de Alencar; Masaharu Ikegaki; Patricia Correa Dias; Carina Denny

• Advisor: Pedro Luiz Rosalen

Abstract

The objective of this study was to evaluate the activity and possible mechanisms of action of compounds isolated from Brazilian propolis on modulation of the inflammatory process. The anti-inflammatory activities of vestitol and neovestitol, isolated from Brazilian red propolis and cinnamoyloxy-mammeisin (CNM), isolated from Melipona scutellaris geopropolis were evaluated and the following results were observed: 1) Vestitol had inhibitory activity against LPS or mBSA induced neutrophil migration as well as on the release of chemokines CXCL1/KC and CXCL2/MIP-2 in vivo and in vitro. It was also found that treatment with vestitol reduced leukocytes rolling and adhesion in mice mesenteric microcirculation. Regarding the activity on neutrophil in vitro, vestitol reduced CXCL2/MIP-2 and LTB4 induced neutrophils chemotaxis and blocked the calcium influx in these cells. No change was observed in CXCR2 receptor expression with vestitol pretreatment. 2) The administration of neovestitol reduced neutrophil migration, leukocytes rolling and adhesion and ICAM-1 expression in mice challenged with LPS. Despite the release of TNF-?, CXCL1/KC and CXCL2/MIP-2, we found no activity of neovestitol on these inflammatory mediators. Furthermore, the compound did not alter the in vitro ICAM-1expression. Moreover, it was observed that administration of a nitric oxide sintase inhibitor abolished the anti-inflammatory effect of neovestitol neutrophils migration. In the of collagen-induced arthritis model, it was found that the daily administration of neovestitol for 12 days, reduced the clinical arthritis score of the animals, joint injury and IL-6 release. 3) Regarding the results obtained with CNM, it was found that administration reduced neutrophil migration into the peritoneal and joint cavity, as well as TNF-? and CXCL2/MIP-2 release in vivo and in vitro. Concerning mechanism of action, it was found that CNM reduced the expression of the phosphorylated proteins ERK 1/2, JNK, p38 MAPK and c-jun in RAW 264.6 macrophages. Furthermore, it was observed that CNM reduced NF-kB activation, however, did not affect the I?B? degradation and p65 nuclear translocation. Thus, we conclude that Brazilian propolis is an important source of active compounds with biological potential. Also, some of isolated compounds such as vestitol, neovestitol and CNM are promising anti-inflammatory agents with distinct mechanisms of action with possible therapeutic use in acute or chronic inflammatory processes (AU)

• FAPESP's process: 12/01365-0 - In vivo and in vitro study of activity of isolated compounds from Brazilian propolis on modulation of neutrophils migration in the inflammatory process
• Grantee: Marcelo Franchin
• Support Opportunities: Scholarships in Brazil - Doctorate