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AIMS: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. METHODS: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1ß level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. RESULTS: Periodontitis significantly increased MPO activity, interleukin-1ß level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1ß level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. CONCLUSION: UMB improved periodontitis by reducing inflammation and bone markers.
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OBJECTIVE: Calotropis procera latex protein (CpLP) is a popular anti-inflammatory and therefore we aimed to study its effects on inflammatory bone loss. DESIGN: Male Wistar rats were subjected to a ligature of molars. Groups of rats received intraperitoneally CpLP (0.3 mg/kg, 1 mg/kg, or 3 mg/kg) or saline (0.9% NaCl) one hour before ligature and then daily up to 11 days, compared to naïve. Gingiva was evaluated by myeloperoxidase activity and interleukin-1 beta (IL-1ß) expression by ELISA. Bone resorption was evaluated in the region between the cement-enamel junction and the alveolar bone crest. The histology considered alveolar bone resorption and cementum integrity, leukocyte infiltration, and attachment level, followed by immunohistochemistry bone markers between 1st and 2nd molars. Systemically, the weight of the body and organs, and a leukogram were performed. RESULTS: The periodontitis significantly increased myeloperoxidase activity and the IL-1ß level. The increased bone resorption was histologically corroborated by periodontal destruction, leukocyte influx, and attachment loss, as well as the increasing receptor activator of the nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio, and Tartrate-resistant acid phosphatase (TRAP)+ cells when compared to naïve. CpLP significantly reduced myeloperoxidase activity, level of IL-1ß, alveolar bone resorption, periodontal destruction, leukocyte influx, and attachment loss. The CpLp also reduced the RANKL/OPG ratio and TRAP+ cells, when compared with the saline group, and did not affect the systemic parameters. CONCLUSIONS: CpLP exhibited a periodontal protective effect by reducing inflammation and restricting osteoclastic alveolar bone resorption in this rat model.
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Perda do Osso Alveolar , Calotropis , Ratos , Masculino , Animais , Ratos Wistar , Látex/farmacologia , Peroxidase , Calotropis/metabolismo , Inflamação/prevenção & controle , Perda do Osso Alveolar/patologia , Osteoprotegerina/farmacologia , Processo Alveolar/metabolismo , Antioxidantes , Ligante RANK/metabolismoRESUMO
BACKGROUND: Members of the botanical families Apiaceae/Umbelliferae, Asteraceae, Fabaceae/Leguminosae, and Thymelaeaceae are rich in coumarins and have traditionally been used as ethnomedicines in many regions including Europe, Asia, and South America. Coumarins are a class of secondary metabolites that are widely present in plants, fungi, and bacteria and exhibit several pharmacological, biochemical, and therapeutic effects. Recently, many plants rich in coumarins and their derivatives were found to affect bone metabolism. OBJECTIVE: To review scientific literature describing the mechanisms of action of coumarins in osteoclastogenesis and bone resorption. MATERIALS AND METHODS: For this systematic review, the PubMed, Scopus, and Periodical Capes databases and portals were searched. We included in vitro research articles published between 2010 and 2020 that evaluated coumarins using osteoclastogenic markers. RESULTS: Coumarins have been reported to downregulate RANKL-RANK signaling and various downstream signaling pathways required for osteoclast development, such as NF-κB, MAPK, Akt, and Ca2+ signaling, as well as pathways downstream of the nuclear factor of activated T-cells (NFATc1), including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase 9 (MMP-9). CONCLUSIONS: Coumarins primarily inhibit osteoclast differentiation and activation by modulating different intracellular signaling pathways; therefore, they could serve as potential candidates for controlled randomized clinical trials aimed at improving human bone health.
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Reabsorção Óssea/tratamento farmacológico , Cumarínicos/farmacologia , Ligante RANK/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Osteogênese/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/fisiologiaRESUMO
The molecular weight of chitosan (CS) may affect its physical properties and its ability to induce an appropriate host response. The biocompatibilities of CS membranes of low (LMWCS) and high (HMWCS) molecular weight were investigated by inserting these materials into the subcutaneous tissue of rats for 1-28 days and evaluating leukocyte infiltration, granulation tissue, fibrosis, arginase-1 immunostaining, as well as nuclear factor-κB (NF-κΒ) and fibroblast growth factor (FGF)-2 expressions. Both CS membranes induced a peak of leukocyte infiltration on the first day of insertion and stimulated granulation and fibrous tissue generation when compared to control. LMWCS induced more collagen deposition a week earlier, when compared to the control and HMWCS membrane. The membranes also increased arginase-1 immunostaining, a M2 macrophage marker. M2 macrophage is recognized as anti-inflammatory and pro-regenerative. NF-κB is an essential biomarker of the inflammatory process and induces the expression of several pro-inflammatory cytokines. The LMWCS membrane reduced inflammation, as indicated by a reduced nucleus/cytoplasm NF-κB ratio in surrounding tissue from days 7 to 14 when compared to control. On the first day, the expression of FGF-2, a biomarker of inflammatory resolution, was increased in the tissue of the LWMCS group, when compared with HMWCS, which was consistent with the type I collagen deposition. Thus, LWMCS was associated with a prior reduction of the inflammatory response and improved wound healing.