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Effect of a novel Chalcone on inflammatory bone resorption in an experimental model of periodontal disease.

Grant number: 18/17047-3
Support type:Regular Research Grants
Duration: November 01, 2018 - April 30, 2021
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Morgana Rodrigues Guimarães Stabili
Grantee:Morgana Rodrigues Guimarães Stabili
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Assoc. researchers:Carlos Rossa Junior ; Luis Carlos Spolidorio ; Luis Octávio Regasini

Abstract

Chalcones are a group of plant-derived phenolic compounds with diverse biological properties such as anti-inflammatory, antioxidant, antimicrobial and anti-resorptive. Due to their pharmacological effects, different natural and synthetic chalcone derivatives have been investigated as therapeutic agents. Clinical and preclinical studies have demonstrated its effectiveness in the treatment of inflammatory diseases such as cancer, arthritis and inflammatory bowel disorders, and in bone pathologies such as osteoporosis and bone tumors; however, its potential in the treatment of periodontal diseases has not yet been investigated. Chalcones can modulate inflammation and bone turnover through different mechanisms, including inhibition of cytokine production, regulation of intracellular signaling pathways, and modulation of the activity of transcription factors, all of which are key factors in the pathogenesis of periodontitis. Considering the biological properties of these compounds, our research group evaluated in vitro the ability of a new chalcone derivative (Chalcona T4), which was tested for the first time, to suppress the expression of relevant mediators in inflammation and osteoclastogenesis. Chalcona T4 was able to reduce the gene expression of inflammatory bone resorption markers in macrophages by more than 90%, in addition to reducing the differentiation of precursor cells in osteoclasts, showing results superior to those presented by other chalcones described in the literature. In addition to the potent anti-inflammatory and anti-resorptive effects demonstrated, Chalcona T4 also has advantages such as high aqueous solubility and low cytotoxicity, which favors its pharmacodynamic characteristics and its use in in vivo models. In order to evaluate the effects of this new compound on the inflammatory bone resorption associated with the periodontal disease model, the aim of this study is to evaluate the effects of this new compound on inflammatory diseases, experimental, and investigate the biological mechanisms involved. Although the effects of chalcones have been reported in other models of inflammatory diseases, this is the first study to evaluate the action of a synthetic chalcone in a model of periodontal disease, as well as the first study to evaluate the Chalcone T4. The hypothesis of this work is that the compound is able to reduce bone resorption and inflammation in a model of experimental periodontal disease, and that this effect involves the modulation of critical biological mediators in osteoclastogenesis, particularly the intracellular signaling pathways NF-8B, MAP Kinases and PI3K-Akt. (AU)