Department of Stomatology, PLA No. 983 Hospital, Tianjin, China.
Folia Histochem Cytobiol. 2024;62(3):145-153. doi: 10.5603/fhc.101862. Epub 2024 Aug 28.
Periodontitis (PD) is a chronic inflammatory disease leading to alveolar bone loss. This study investigated the effect of nootkatone and regulatory mechanism in reducing periodontal inflammation and alveolar bone loss in a rat model.
Twenty male Sprague-Dawley rats were divided into control, periodontitis, and nootkatone-treated groups (45 or 90 mg/kg). Ligature induction method was adopted to establish the PD model. After 21 days, rats received daily gavage of either saline or nootkatone for 10 days. Alveolar bone loss was assessed using micro-CT. Histological analyses included hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Masson's trichrome stainings. Immunohistochemistry for heme oxygenase 1 (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2) were performed in periodontal tissues. Content of inflammatory cytokines IL-1β, IL-6, and TNF-α in gingival tissues around ligature were assessed using ELISA kits. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were analyzed and Western blot for NF-κB expression in gingival tissues were performed.
Nootkatone significantly reduced the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC), enhanced bone mineral density (BMD), bone volume (BV), and BV/total volume (TV) ratio in ligature-induced rats. Higher dose of nootkatone (90 mg/kg) did not show more significant therapeutic effect than lower dose (45 mg/kg). Histological staining showed decreased osteoclasts' number and improved bone architecture in the nootkatone group. Content of IL-1β, IL-6, and TNF-α and inflammatory cell infiltration level in gingival tissues around the ligature were decreased in the nootkatone-treatment rats. Nootkatone increased Nrf2 and HO-1 protein expression and decreased NF-κB protein level, suppressing MDA levels and enhancing SOD activity.
In a rat model, nootkatone effectively mitigates periodontal inflammation and alveolar bone loss through the Nrf2/HO-1 and NF-κB pathways. These findings suggest nootkatone as a promising therapeutic agent for the treatment of periodontitis.
牙周炎（PD）是一种导致牙槽骨丧失的慢性炎症性疾病。本研究通过建立大鼠模型，探讨了诺卡酮在减轻牙周炎炎症和牙槽骨丧失中的作用及其调控机制。
将 20 只雄性 Sprague-Dawley 大鼠分为对照组、牙周炎组和诺卡酮治疗组（45 或 90mg/kg）。采用结扎诱导法建立 PD 模型。21 天后，大鼠每天给予生理盐水或诺卡酮灌胃 10 天。采用微 CT 评估牙槽骨丧失情况。对苏木精-伊红（H&E）、抗酒石酸酸性磷酸酶（TRAP）和 Masson 三色染色进行组织学分析。对牙周组织进行血红素加氧酶 1（HO-1）和核因子红细胞 2 相关因子 2（Nrf2）的免疫组织化学染色。采用 ELISA 试剂盒检测结扎周围牙龈组织中炎症细胞因子 IL-1β、IL-6 和 TNF-α的含量。分析牙龈组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）水平，并进行 NF-κB 表达的 Western blot 分析。
诺卡酮显著降低了牙骨质-牙槽骨交界（CEJ-ABC）至牙槽骨嵴的距离，提高了结扎诱导大鼠的骨矿物质密度（BMD）、骨体积（BV）和 BV/总容积（TV）比值。高剂量（90mg/kg）的诺卡酮治疗效果并不优于低剂量（45mg/kg）。组织学染色显示，诺卡酮组破骨细胞数量减少，骨结构改善。结扎周围牙龈组织中 IL-1β、IL-6 和 TNF-α含量及炎症细胞浸润水平降低。诺卡酮增加了 Nrf2 和 HO-1 蛋白表达，降低了 NF-κB 蛋白水平，抑制了 MDA 水平，提高了 SOD 活性。
在大鼠模型中，诺卡酮通过 Nrf2/HO-1 和 NF-κB 途径有效减轻牙周炎炎症和牙槽骨丧失。这些发现表明诺卡酮有望成为治疗牙周炎的一种有前途的治疗药物。
