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

• Grant number: 12/01365-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2012
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Pedro Luiz Rosalen
• Grantee: Marcelo Franchin
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

The extensive neutrophil migration and the consequent tissue damage are present in several inflammatory diseases. Therefore, the search for drugs that interfere with the traffic of neutrophils in the inflammatory process has been increasing. Initial studies of our research group with neovestitol and vestitol, compounds isolated from propolis type 13 (red), and a bioactive fraction identified of geopropolis of Melipona scutellaris, showed promising on inhibition of neutrophil migration. However, more studies are necessary for the isolation and identification of compound responsible by activity of bioactive fraction, as well as demonstrate the efficiency of these isolated compounds on inhibition of migration neutrophils, followed by elucidation of their mechanisms of action. The objective of this study is to evaluate the activity and possible mechanisms of compounds isolated from Brazilian propolis on modulation of neutrophil migration in inflammatory process. The study will be conducted in two stages: the first will be made by the isolation of bioactive compounds (neovestitol and vestitol) of propolis, as well as the isolation and identification of bioactive compound of geopropolis fraction; in the second stage, will be applied biological assays with the isolated compounds of both propolis, where the activity will be evaluated on: migration of neutrophils induced by LPS or mBSA; leukocyte rolling and adhesion in venular endothelium; synthesis and/or liberation of inflammatory mediators in vivo; expression of molecules like P-selectin, ICAM-1 (present at endothelial cells); neutrophils chemotaxis in vitro; synthesis and/or liberation of inflammatory mediators by neutrophils production; the intracellular signaling pathways, the expression of Toll-like receptor (TLR) 2 and TLR4, the intracellular levels of calcium and the expression of B2-integrin in neutrophils in vitro. It is expected that this study could obtain bioactive compounds isolated from two varieties of Brazilian propolis, capable of inhibiting neutrophil migration induced by different inflammatory stimuli and has your mechanism of action elucidated. Furthermore, these new information could contribute for the use of these compounds as a novel anti-inflammatory agents or prototypes of new drugs.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRANCHIN, MARCELO; COLON, DAVID F.; CASTANHEIRA, FERNANDA V. S.; DA CUNHA, MARCOS G.; BUENO-SILVA, BRUNO; ALENCAR, SEVERINO M.; CUNHA, THIAGO M.; ROSALEN, PEDRO L.. Vestitol Isolated from Brazilian Red Propolis Inhibits Neutrophils Migration in the Inflammatory Process: Elucidation of the Mechanism of Action. Journal of Natural Products, v. 79, n. 4, p. 954-960, APR 2016. (12/22378-2, 13/08216-2, 12/01365-0)

FRANCHIN, MARCELO; COLON, DAVID F.; DA CUNHA, MARCOS G.; CASTANHEIRA, FERNANDA V. S.; SARAIVA, ANDRE L. L.; BUENO-SILVA, BRUNO; ALENCAR, SEVERINO M.; CUNHA, THIAGO M.; ROSALEN, PEDRO L.. Neovestitol, an isoflavonoid isolated from Brazilian red propolis, reduces acute and chronic inflammation: involvement of nitric oxide and IL-6. SCIENTIFIC REPORTS, v. 6, NOV 7 2016. (12/22378-2, 13/08216-2, 12/01365-0)

FRANCHIN, MARCELO; ROSALEN, PEDRO LUIZ; DA CUNHA, MARCOS GUILHERME; SILVA, RANGEL LEAL; COLON, DAVID F.; BASSI, GABRIEL SHIMIZU; DE ALENCAR, SEVERINO MATIAS; IKEGAKI, MASAHARU; ALVES-FILHO, JOSE C.; CUNHA, FERNANDO Q.; et al. Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-kappa B. Journal of Natural Products, v. 79, n. 7, p. 1828-1833, JUL 2016. (12/22378-2, 13/08216-2, 12/01365-0)

BUENO-SILVA, BRUNO; FRANCHIN, MARCELO; ALVES, CLAUDINEY DE FREITAS; DENNY, CARINA; COLON, DAVID FERNANDO; CUNHA, THIAGO MATTAR; ALENCAR, SEVERINO MATIAS; NAPIMOGA, MARCELO HENRIQUE; ROSALEN, PEDRO LUIZ. Main pathways of action of Brazilian red propolis on the modulation of neutrophils migration in the inflammatory process. Phytomedicine, v. 23, n. 13, p. 1583-1590, DEC 1 2016. (12/22378-2, 12/01500-4, 12/01365-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FRANCHIN, Marcelo. In vivo and in vitro activity of isolated compounds from Brazilian propolis on the modulation of the inflammatory process. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Campinas, SP.