Hesperidin is a glycoside belonging to the subclass of flavonones, found abundantly in citrus fruits, and has multiple biological properties, and its pharmacological actions are often reviewed as they appear to have beneficial effects on the prevention and complications of diabetes mellitus and dyslipidemias as well as to show anti-inflammatory and antioxidant properties. This potential, coupled with the virtual absence of cytotoxicity, makes this compound of interest and potential for health-related applications. Reports of hesperidin's anti-inflammatory and antioxidant activity are variable but include promising information on some types of diseases such as cancer and osteoporosis. However, information regarding the therapeutic potential of hesperidin specifically in chronic inflammatory diseases such as that affecting the periodontium is scarce. The established hypothesis is that hesperidin promotes osteogenesis, blocks osteoclastogenesis and reduces the inflammatory response, and has a therapeutic effect on periodontitis. Therefore, the following objectives were established: Specific objective #1: To evaluate, in vitro, the action of the hesperidin on osteogenesis, osteoclastogenesis and production of inflammatory mediators. Experimental approach - Raw 264.7 and MC3T3-E1 cells will be used. The cells will be submitted to the doses of 1, 100 and 500 ¼M hesperidin in experiments that will evaluate the differentiation and function of osteoblasts (evaluating the expression of genes regulating bone metabolism, formation of mineralized nodules, organization and maturation of collagen), osteoclastogenesis (evaluating the differentiation of osteoclasts by TRAP, osteoclast activity and reabsorption points), and evaluation of the expression of inflammatory mediators in stimulated macrophages, using Bioplex 200. Specific objective #2: To evaluate, in vivo, the therapeutic action of hesperidin on experimental periodontitis in mice. Experimental approach - A model of periodontal disease will be used by injecting bacteria around the maxillary molars in mice. After the experimental period of induction of the disease, the mice will be treated with 1¼M 100¼M or 500¼M hesperidin by oral gavage. The animals will be euthanized and the samples collected for analysis of the bone volume, through computerized microtomography - ¼CT; stereometric analysis of the gingival inflammatory process in histological sections stained by H&E; and of osteoclasts by immunohistochemistry of TRAP.
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