Plant and Fungal Polysaccharides in Periodontitis Treatment: Diverse Mechanisms and Therapeutic Roles.

Background: Periodontitis is a chronic immune-mediated inflammatory disease characterized by the progressive degradation of periodontal tissues. Conventional therapies, including anti-inflammatory agents and antibiotics, are limited by systemic adverse effects and increased microbial resistance, highlighting the need for safer, multi-targeted treatments. Objective: This review systematically evaluates the therapeutic potential of plant- and fungal-derived polysaccharides in periodontitis treatment. It focuses on their multifaceted biological activities, including anti-inflammatory, antioxidant, antimicrobial, and osteo-regenerative effects, and elucidates key molecular mechanisms, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF- Materials and Methods: A systematic literature search was performed across PubMed, Scopus, Web of Science, and Google Scholar databases using a combination of Medical Subject Heading (MeSH) terms and keywords, including "periodontitis," "plant polysaccharides," "fungal polysaccharides," "inflammatory factors," and "bone regeneration." A total of 104 studies were included after screening for relevance to the therapeutic roles and molecular mechanisms of plant- and fungal-derived polysaccharides in periodontitis. The dataset encompassed both in vitro and in vivo investigations, and narrative synthesis was employed to integrate findings owing to the substantial heterogeneity in study designs, endpoints, and methodological approaches. Conclusion: Plant- and fungal-derived polysaccharides have substantial potential as adjunct or alternative therapies for the treatment of periodontitis. Their multifunctional activities, including modulation of inflammation, inhibition of pathogenic biofilms, and promotion of periodontal tissue regeneration, are mediated through complex multi-pathway interactions. Clinical translation remains limited by structural heterogeneity, a lack of standardized preparation protocols, and insufficient in vivo validation. Future research should prioritize elucidating structure-activity relationships, optimizing extraction and formulation methods, and conducting well-designed clinical trials. Integrating evidence from 104 studies, this review underscores the anti-inflammatory, antimicrobial, and osteo-regenerative effects of these polysaccharides and emphasizes their importance in future clinical applications.