Characterization of new pharmacological targets and study of the activity of a 4-phenyl coumarin in the differentiation of Th17 lymphocytes in the development of periodontal disease

• Grant number: 16/15563-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2017
• End date: December 26, 2019
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• 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

T helper lymphocytes 17 (Th17) play a key role in the development of periodontal disease due to its pro-inflammatory effects, becoming a promising target for the discovery of new drugs for the treatment of this disease. In the present study we aim to characterize new pharmacological targets and study the activity of cinnamoyloxy-mammeisin (CNM, a 4-phenyl coumarin) on the differentiation of Th17 lymphocytes in the development of periodontal disease. The present study is divided into 5 steps: 1) Characterization of the participation of Th17 lymphocytes (analysis of the frequency of IL17A and quantification of IL-17 and IL-22) and its main signaling pathways (Stat3, pStat3, Jak2, pJak2 , Socs3 and SHP1 by western blotting and gene expression of Rora, Rorc, IL17a, IL21, IL22 and IL23r) in the mice model of periodontitis induced by Porphyromonas gingivalis; 2) Conducting pharmacogenomic and bioinformatics tests for the characterization of new pharmacological targets that may be involved in the differentiation of Th17 lymphocytes during the development of experimental periodontal disease; 3) In vitro evaluation of CNM activity and mechanisms of action in naive T lymphocytes isolated from mice and differentiated for Th17; 4) In vivo activity of CNM in the differentiation of Th17 lymphocytes and in the development of periodontal disease induced by P. gingivalis in mice; And finally in the last step, 5) it will be tested the activity of CNM on differentiation of Th17 lymphocytes in human cells. This study seeks to characterize the participation of the main signaling pathways (kinases and phosphatases) involved in the differentiation of Th17 lymphocytes in the model of experimental periodontal disease. Also, to find new pharmacological targets involved in this event and propose a new naturally occurring drug which shows inhibitory activity in the development of periodontal disease by modulating the differentiation of Th17 lymphocytes. (AU)

Scientific publications

(7)

(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)

DE CAMARGO, ADRIANO COSTA; SCHWEMBER, ANDRES R.; PARADA, ROBERTO; GARCIA, SANDRA; MAROSTICA JUNIOR, MARIO ROBERTO; FRANCHIN, MARCELO; BISMARA REGITANO-D'ARCE, MARISA APARECIDA; SHAHIDI, FEREIDOON. Opinion on the Hurdles and Potential Health Benefits in Value-Added Use of Plant Food Processing By-Products as Sources of Phenolic Compounds. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 11, NOV 2018. (12/17683-0, 15/50333-1, 16/15563-9, 15/00336-4)

FRANCHIN, MARCELO; TAIRA, THAISE MAYUMI; PRADO, DOUGLAS DA SILVA; SPECK HERNANDEZ, CESAR AUGUSTO; DE ANDRADE, FABIO BONIFACIO; ABDALLA, HENRIQUE BALLASSINI; NAPIMOGA, MARCELO HENRIQUE; CUNHA, THIAGO MATTAR; FUKADA, SANDRA YASUYO; ROSALEN, PEDRO LUIZ. PI3K gamma controls IL-17A expression and attenuates alveolar bone loss in an experimental periodontitis model. Inflammation Research, v. 72, n. 1, p. 8-pg., 2022-11-04. (17/09898-0, 16/15563-9)

FRANCHIN, MARCELO; FREIRES, IRLAN ALMEIDA; LAZARINI, JOSY GOLDONI; NANI, BRUNO DIAS; DA CUNHA, MARCOS GUILHERME; COLON, DAVID FERNANDO; DE ALENCAR, SEVERINO MATIAS; ROSALEN, PEDRO LUIZ. The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 153, n. SI, p. 49-55, JUN 10 2018. (16/02926-6, 16/15563-9, 15/26864-7)

FALCAO, HELOISA GABRIEL; RAMOS SILVA, MARIAH BENINE; DE CAMARGO, ADRIANO COSTA; SHAHIDI, FEREIDOON; FRANCHIN, MARCELO; ROSALEN, PEDRO LUIZ; ALENCAR, SEVERINO MATIAS; KUROZAWA, LOUISE EMY; IDA, ELZA IOUKO. Optimizing the potential bioactivity of isoflavones from soybeans via ultrasound pretreatment: Antioxidant potential and NF-kappa B activation. JOURNAL OF FOOD BIOCHEMISTRY, v. 43, n. 11, AUG 2019. (16/15563-9, 17/09898-0)

DE CAMARGO, ADRIANO COSTA; TELLES BIASOTO, ALINE CAMARAO; SCHWEMBER, ANDRES R.; GRANATO, DANIEL; RASERA, GABRIELA BOSCARIOL; FRANCHIN, MARCELO; ROSALEN, PEDRO L.; ALENCAR, SEVERINO MATIAS; SHAHIDI, FEREIDOON. Should we ban total phenolics and antioxidant screening methods? The link between antioxidant potential and activation of NF-kappa B using phenolic compounds from grape by-products. Food Chemistry, v. 290, p. 229-238, AUG 30 2019. (16/15563-9)

DE CAMARGO, ADRIANO COSTA; SCHWEMBER, ANDRES R.; PARADA, ROBERTO; GARCIA, SANDRA; MAROSTICA JUNIOR, MARIO ROBERTO; FRANCHIN, MARCELO; BISMARA REGITANO-D'ARCE, MARISA APARECIDA; SHAHIDI, FEREIDOON. Opinion on the Hurdles and Potential Health Benefits in Value-Added Use of Plant Food Processing By-Products as Sources of Phenolic Compounds. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 11, p. 47-pg., 2018-11-01. (15/50333-1, 16/15563-9, 12/17683-0, 15/00336-4)

FRANCHIN, MARCELO; FREIRES, IRLAN ALMEIDA; LAZARINI, JOSY GOLDONI; NANI, BRUNO DIAS; DA CUNHA, MARCOS GUILHERME; COLON, DAVID FERNANDO; DE ALENCAR, SEVERINO MATIAS; ROSALEN, PEDRO LUIZ. The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 153, p. 7-pg., 2018-06-10. (15/26864-7, 16/15563-9, 16/02926-6)