The Critical Role of Polyphenols in Immunomodulation and Periodontal Regeneration

ABSTRACT Objectives Periodontitis, the main cause of tooth loss in adults, is a widespread oral disease characterized by chronic inflammation primarily triggered by periodontopathic bacterial infection. Polyphenols are a class of compounds extracted from herbs and diets, characterized by the presence of more than one phenol unit per molecule. Emerging evidence has revealed that polyphenols show significant effectiveness in ameliorating tissue destruction in periodontitis. Herein, we comprehensively review current literature studying the critical role of polyphenols in periodontitis and summarize the predominant molecular mechanisms in immunomodulation and periodontal regeneration, aiming to provide a better understanding of their therapeutic potential in periodontitis. Methods PubMed and Web of Science databases were searched for articles, reviews, and clinical studies published until August 2024. Results We summarized the immunomodulatory effects of polyphenols in vivo and in vitro, described the research advance regulating the functions of periodontal ligament stem cells and their regeneration potential, and discussed the underlying mechanisms. Finally, we propose future directions for periodontitis therapies with polyphenols. Conclusions Polyphenols exert a significant anti‐inflammatory effect and promising potential to promote periodontal regeneration. Further study of the molecular mechanisms and techniques to increase the bioavailability and effect of polyphenols is warranted.