Resveratrol adjunct therapy reduces pro-inflammatory cytokines, attenuates alveolar bone loss, and improves clinical markers in **periodontal disease**.

Periodontal disease is a chronic inflammatory condition affecting the tissues supporting the teeth, leading to progressive attachment loss and alveolar bone destruction. It is primarily initiated by bacterial biofilms but exacerbated by host inflammatory responses. Current standard-of-care, such as root planing, effectively removes biofilm but often benefits from adjunctive therapies to modulate inflammation and enhance tissue regeneration. Resveratrol, a natural polyphenol, has garnered interest due to its well-documented anti-inflammatory and antioxidant properties, making it a promising candidate to address the inflammatory cascade central to periodontal pathology.

This systematic review and meta-analysis synthesized evidence from 15 studies: five in vitro cell models, six in vivo experimental periodontitis models, and five human randomized controlled trials (RCTs). Researchers conducted electronic searches across MEDLINE/PubMed, Scopus, Embase, and Web of Science for studies published between 2000 and 2025. Eligible clinical trials focused on systemically healthy non-smoking patients. Data extraction, risk-of-bias assessment, and meta-analyses were performed following PRISMA guidelines to evaluate the effects of resveratrol as an adjunctive therapy.

Meta-analysis of in vitro studies demonstrated a significant inhibitory effect of resveratrol on lipopolysaccharide-induced protein expression of pro-inflammatory cytokines: IL-1β, IL-6, TNF-α, and IL-8, with low to moderate heterogeneity. In animal models, resveratrol consistently and significantly attenuated ligature-induced dental alveolar bone loss and reduced IL-1β protein and relative mRNA expression. However, reductions in relative mRNA expressions of TNF-α and IL-6 were inconsistent and highly heterogeneous across animal studies. Notably, nanoparticle- and liposomal-modified resveratrol formulations consistently and significantly reduced these mRNA levels. In human trials, adjunctive resveratrol was associated with significant improvements compared to root planing alone:

Probing pocket depth and clinical attachment level improved in patients with periodontitis, alongside reductions in bleeding and plaque indices in patients with periodontal diseases, including gingivitis and periodontitis.