Polygonati Rhizoma Attenuates Oxidative Stress-Induced Senescence in Periodontal Ligament Stem Cells

Periodontitis is increasingly recognized as a non-communicable chronic oral disease in which sustained oxidative stress and cellular senescence drive low-grade inflammation and tissue destruction. Polygonati Rhizoma (PR), a traditional Chinese herb widely consumed as a functional food ingredient, is rich in antioxidant polyphenols and polysaccharides, yet its role in modulating senescence of periodontal ligament stem cells (PDLSCs) remains unclear. This study integrated network pharmacology and experimental validation to elucidate the protective effects and mechanisms of PR against oxidative stress-induced PDLSC senescence. Putative PR components and targets related to periodontitis and aging were collected to construct a protein-protein interaction (PPI) network, from which 21 core targets were predicted. These included key inflammation- and senescence-related proteins such as TP53, RELA (p65), TNF-α, TGF-β1, IL-6, IL-1β, CXCL8, and MMP-9. Gene Ontology and KEGG enrichment analyses highlighted pathways involved in cellular senescence, NF-κB signaling, and oxidative stress responses. Molecular docking suggested strong binding affinities between major PR constituents and putative core protein targets. In an in vitro oxidative stress-induced PDLSC senescence model, PR-medicated serum, with Metformin as a positive control, significantly reduced intracellular oxidative stress markers, alleviated cell-cycle arrest, and downregulated senescence-associated secretory phenotype (SASP) cytokines. PR showed anti-senescent efficacy comparable to Metformin while exhibiting distinct molecular signatures. These findings indicate that PR exerts multi-component, multi-target modulation of NF-κB-centered inflammatory and senescence pathways in PDLSCs, thereby mitigating oxidative stress-induced cellular aging. As an edible, functional herb, PR may represent a promising dietary adjunct for the prevention and management of periodontitis linked to cellular senescence.