Beyond Antioxidant: The Multifaceted Role of Resveratrol as an Antibacterial, Immunomodulatory, and Pro‐Regenerative Agent in Periodontitis
Yu‐Jie Tan, Mei Xu, Yue‐Hua Ran, Nan Jia, Rui‐Xin Wu, Bei‐Min Tian, Fa‐Ming ChenABSTRACT
Objective
Periodontitis treatment centers on three pillars: antibacterial, anti‐inflammatory, and regenerative approaches. This review aims to demonstrate that resveratrol (RSV) simultaneously targets all three core components, positioning it as a multifunctional disease‐modifying agent.
Methods
We conducted a narrative review of RSV in periodontitis by searching PubMed and Web of Science from inception to July 2026. Rather than focusing solely on its well‐established antioxidant properties, we comprehensively investigated its multifaceted mechanisms across the three key pathological dimensions.
Results
RSV demonstrates broad‐spectrum antibacterial activity by inhibiting biofilm formation, suppressing bacterial ATP synthase, inducing DNA damage, and disrupting efflux pumps to counteract antibiotic resistance. RSV modulates host immune responses through multiple signaling pathways, primarily via SIRT1‐mediated epigenetic regulation. RSV also interacts with immune cells and regulates innate immune memory, thereby reducing the risk of disease recurrence associated with trained immunity‐induced hyperinflammation. Furthermore, RSV orchestrates stem cell recruitment via SDF‐1α signaling and cytoskeletal reorganization, while directing cell differentiation through mitochondrial quality control and epigenetic modifications, thereby promoting endogenous periodontal regeneration.
Conclusions
This review provides a comprehensive analysis of the multifaceted roles of RSV in antibacterial action, immunomodulation, and tissue regeneration, highlighting its potential as a multifunctional agent against the complex pathological progression of periodontitis.