Antimicrobial and anti-inflammatory evaluation of a new chalcone compound in a model of experimental periodontal disease in rats

Abstract

Chalcones are a group of phenolic compounds derived from plants, with various biological properties such as anti-inflammatory, 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, but its role in periodontal disease 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. In addition to anti-inflammatory activity, chalcones can also eliminate a number of oral bacteria, including Phorphyromonas gingivalis (Pg), and inhibit the formation of biofilm formed by gram-negative anaerobic bacteria. 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. Considering the antibacterial potential demonstrated by some chalcone compounds, it is possible that Chalcona T4 has, besides the anti-inflammatory effect, the ability to inhibit certain bacterial populations, favoring the therapy of inflammatory diseases whose pathogenesis is associated with this etiological agent, such as diseases periodontal diseases. The aim of this study is to evaluate the antimicrobial and anti-inflammatory potential of the systemic administration of chalcone T4 in a disease model. The hypothesis of this project is that Chalcone T4 can act by reducing the number of periodontopathogenic bacteria and the presence of inflammatory process in the periodontal tissues, favoring the resolution of periodontal disease. This hypothesis will be tested through the following specific objectives:Specific objective # 1: To evaluate the effect of systemic administration of chalcone T4 on the suppression of periodontopathogenic bacteria in a model of experimental periodontal disease in rats: the ligatures will be used to evaluate the presence of Pg, Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans (Aa) and Fusobacterium nucleatum (Fn) through the PCR reaction;Specific objective # 2: To analyze the histopathological characteristics of the gingival tissues treated or not treated with the compound and to correlate with the microbiological data. The proportion of the cellular components (inflammatory cells and fibroblasts, blood vessels, collagen fibers) will be evaluated by stereometric analysis.