State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200001, China.
Int Immunopharmacol. 2024 Nov 15;141:112933. doi: 10.1016/j.intimp.2024.112933. Epub 2024 Aug 25.
Periodontitis is a chronic inflammatory disease that affects about 45 %-50 % of adults worldwide, but the efficacy of current clinical therapies is unsatisfactory due to the complicated periodontal immune microenvironment. Thus, developing drugs that can regulate innate immune cells (e.g., macrophages) is a potent strategy to treat periodontitis. Here, we report that phloretin, a food plant-derived natural compound, is sufficient to alleviate periodontitis through immune regulation. In vivo, phloretin treatment could significantly reduce alveolar bone resorption and periodontal inflammation in mouse periodontitis models. In vitro, phloretin could suppress proinflammatory (M1-like) polarization and cytokine release in macrophages induced by LPS. Mechanistically, the immune regulatory role of phloretin in macrophages may be due to its metabolic regulation effect. Phloretin might restore the balance of M1/M2 macrophage transition in periodontitis by inhibiting HIF-1α-mediated glycolysis and PI3k/Akt pathways, thereby reducing the proinflammatory effect and immune disorder caused by over-activated M1 macrophages. Together, this study highlights that natural compound, such as phloretin, can restore periodontal immune homeostasis by metabolic regulation of macrophages, which may provide novel insight into the treatment of periodontitis.
牙周炎是一种慢性炎症性疾病，影响全球约 45%-50%的成年人，但由于牙周复杂的免疫微环境，目前的临床治疗效果并不理想。因此，开发能够调节固有免疫细胞（如巨噬细胞）的药物是治疗牙周炎的有效策略。在这里，我们报告称，根皮素是一种来源于植物的天然化合物，通过免疫调节足以缓解牙周炎。在体内，根皮素治疗可显著减少小鼠牙周炎模型中牙槽骨吸收和牙周炎症。在体外，根皮素可抑制 LPS 诱导的巨噬细胞中促炎（M1 样）极化和细胞因子释放。在机制上，根皮素在巨噬细胞中的免疫调节作用可能与其代谢调节作用有关。根皮素可能通过抑制 HIF-1α 介导的糖酵解和 PI3k/Akt 途径，恢复牙周炎中 M1/M2 巨噬细胞转化的平衡，从而减轻过度激活的 M1 巨噬细胞引起的促炎作用和免疫紊乱。总之，这项研究强调了天然化合物（如根皮素）可以通过代谢调节巨噬细胞来恢复牙周免疫稳态，这可能为牙周炎的治疗提供新的思路。
