Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor‐kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro‐inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti‐inflammatory property, this study aimed to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll‐like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88)‐mediated pro‐inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin was intraperitoneally injected for consecutive 28 days. Biochemical and enzyme‐linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1β, interleukin 6, and tumor necrosis factor‐α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity was further evaluated by scanning electron microscopy, micro‐computed tomography, and energy‐dispersive X‐ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity, and pro‐inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pretreated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88‐mediated pro‐inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD‐induced destructive damage.

中文翻译：

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褪黑素预防性补充通过正常化RANKL / OPG比并抑制TLR4 / MyD88信号通路成功抑制了牙周炎的发病机理

牙周炎（PD）是一种以牙龈发炎和牙槽骨吸收为特征的炎性疾病。促炎性细胞因子产生的增加导致核因子κB配体/骨保护素（RANKL / OPG）信号转导的受体受损，在PD的发病机理中起着至关重要的作用。考虑到褪黑激素具有显着的抗炎特性，本研究旨在确定褪黑激素的预防性治疗是否可以有效地使RANKL / OPG信号正常化，抑制Toll样受体4 /髓样分化因子88（TLR4 / MyD88）介导的促炎性细胞因子激活，并成功抑制PD的发病机理。通过将结扎线置于磨牙龈下区域诱导成年大鼠PD。PD诱导前14天，10、50，连续28天腹膜内注射100毫克/千克褪黑激素。生化和酶联免疫吸附法分别用于检测TLR4 / MyD88活性，RANKL，OPG，白介素1β，白介素6和肿瘤坏死因子-α水平。骨丢失的程度，骨矿物质强度和钙强度进一步通过扫描电子显微镜，显微计算机断层扫描和能量分散X射线光谱法进行了评估。结果表明，PD后检测出高RANKL / OPG比，TLR4 / MyD88活性和促炎细胞因子水平。生化结果受损与严重的骨质流失和钙强度降低密切相关。但是，在用褪黑素预处理的大鼠中，在接受100 mg / kg的大鼠中，上述所有参数均成功恢复至接近正常水平，并观察到最大变化。由于褪黑激素的预防性治疗可通过抑制TLR4 / MyD88介导的促炎细胞因子的产生有效地使RANKL / OPG信号正常化，因此褪黑激素的膳食补充剂可作为增强口腔健康以抵抗PD引起的破坏性损害的先进策略。