Postgraduate Program in Health Sciences, Federal University of Ceará, Sobral, Ceará, Brazil.
School of Dentistry, Federal University of Ceará, Sobral, Ceará, Brazil.
Clin Oral Investig. 2022 Feb;26(2):1701-1711. doi: 10.1007/s00784-021-04143-9. Epub 2021 Aug 19.
This study aimed to evaluate the anti-resorptive activity of a semi-synthetic coumarin derivative from Platymiscium floribundum, named 6,7-dimethoxy-3-nitrocoumarin.
Molecular docking studies were performed to test the binding performance of the derivative against targets associated with alveolar bone loss (TNF-α, IL-1β, and catalase) and a target considered an antioxidant defense (HO-1) during periodontitis. Periodontitis was induced by placing a nylon ligature around the second molars. The rats received for 11 days 6,7-dimethoxy-3-nitrocoumarin (0.01, 0.1, or 1 mg/kg) or vehicle. We investigated by RT-qPCR analysis (TNF-α, IL-1β, and HO-1 mRNA expression levels) and by colorimetric assay (catalase activity) the mechanism of action mediated by 6,7-dimethoxy-3-nitrocoumarin. The in vivo toxicity of 6,7-dimethoxy-3-nitrocoumarin was evaluated.
6,7-Dimethoxy-3-nitrocoumarin (0.1 or 1 mg/kg) reduced alveolar bone loss (1.05 ± 0.24), when compared to vehicle-treated group (3.05 ± 0.30). The interactions of 6,7-dimethoxy-3-nitrocoumarin and the four targets (TNF-α, IL-1β, catalase, and HO-1) showed firm bonds above 6.0 kcal/mol. 6,7-dimethoxy-3-nitrocoumarin (1 mg/kg) lowered mRNA expression levels of TNF-α (2.33 ± 0.56) and IL-1β (19.87 ± 2.9), while it increased both the mRNA expression levels of HO-1 (43.40 ± 1.05) and the catalase activity (46.42 ± 4.59), when compared to vehicle-treated group (46.29 ± 8.43; 37.83 ± 4.38; 1.58 ± 0.11; 8.93 ± 1.86, respectively). The animals did not show any signs of toxicity.
6,7-Dimethoxy-3-nitrocoumarin decreased inflammatory bone loss in the ligature-induced periodontitis in rats, and the activation of the HO-1 pathway may contribute, at least partially, to its protective effects by reducing TNF-α and IL-1β mRNA levels and increasing catalase activity.
6,7-Dimethoxy-3-nitrocumarin could be used as an adjunct to subgingival instrumentation during active and supportive periodontal treatment.
本研究旨在评估从 Platymiscium floribundum 中提取的半合成香豆素衍生物 6,7-二甲氧基-3-硝基香豆素的抗吸收活性。
进行分子对接研究，以测试该衍生物与牙槽骨丢失相关的靶点（TNF-α、IL-1β和过氧化氢酶）以及被认为是抗氧化防御的靶点（HO-1）的结合性能，以检测在牙周炎期间。通过将尼龙结扎线置于第二磨牙周围来诱导牙周炎。大鼠连续 11 天接受 6,7-二甲氧基-3-硝基香豆素（0.01、0.1 或 1mg/kg）或载体治疗。通过 RT-qPCR 分析（TNF-α、IL-1β和 HO-1 mRNA 表达水平）和比色测定法（过氧化氢酶活性）研究 6,7-二甲氧基-3-硝基香豆素介导的作用机制。评估了 6,7-二甲氧基-3-硝基香豆素的体内毒性。
与载体处理组（3.05±0.30）相比，6,7-二甲氧基-3-硝基香豆素（0.1 或 1mg/kg）降低了牙槽骨丢失（1.05±0.24）。6,7-二甲氧基-3-硝基香豆素与四个靶点（TNF-α、IL-1β、过氧化氢酶和 HO-1）的相互作用显示出超过 6.0kcal/mol 的牢固结合。6,7-二甲氧基-3-硝基香豆素（1mg/kg）降低了 TNF-α（2.33±0.56）和 IL-1β（19.87±2.9）的 mRNA 表达水平，同时增加了 HO-1（43.40±1.05）和过氧化氢酶活性（46.42±4.59）的 mRNA 表达水平，与载体处理组（46.29±8.43；37.83±4.38；1.58±0.11；8.93±1.86，分别）。动物没有表现出任何毒性迹象。
6,7-二甲氧基-3-硝基香豆素可减少结扎诱导的大鼠牙周炎中的炎症性骨丢失，HO-1 途径的激活可能通过降低 TNF-α和 IL-1β mRNA 水平和增加过氧化氢酶活性来部分有助于其保护作用。
6,7-二甲氧基-3-硝基香豆素可在牙周炎的主动和支持性治疗期间作为龈下器械的辅助剂使用。
