2. Academic Validation
  3. Natural compound phloretin restores periodontal immune homeostasis via HIF-1α-regulated PI3K/Akt and glycolysis in macrophages

Natural compound phloretin restores periodontal immune homeostasis via HIF-1α-regulated PI3K/Akt and glycolysis in macrophages

  • Int Immunopharmacol. 2024 Nov 15:141:112933. doi: 10.1016/j.intimp.2024.112933.
Xinyi Zeng 1,  Tiancheng Li 2,  Kuan Yang 1,  Yukun Jiang 1,  Shuo Chen 1,  Shuxian Yang 1,  Shujuan Zou 1,  Jingping Liu 3,  Peipei Duan 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 NHC Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
  • 4 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. Electronic address: duanp@scu.edu.cn.
PMID: 39186834 DOI: 10.1016/j.intimp.2024.112933
Abstract

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.

Keywords

Alveolar bone loss; Immune homeostasis; Inflammation; Macrophages; Metabolism; Periodontal diseases.

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