Lycium Barbarum Glycopetide Remodeling Periodontal Immunopathology By Macrophage Metabolic Reprogramming

Periodontitis is characterized by excessive inflammation and alveolar bone loss driven by imbalanced osteoimmune interactions. Lycium barbarum glycopetide (LbGP), a polysaccharide extract of the Lycium barbarum fruit, has superior anti-inflammatory capacity and biosafety. Here, we focused on the therapeutic potential and underlying mechanisms of LbGP in remodeling periodontal immunopathology. In vivo experiments were performed with the treatment of LBP in the rat experimental periodontitis model. MicroCT scanning and histological analysis were conducted to evaluate periodontal inflammation and osteogenesis in situ. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating the periodontal bone immune microenvironment. In vitro assays evaluated lipid metabolism and inflammatory responses in macrophages, as well as osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) LbGP administration significantly alleviated bone loss and periodontal tissue damage in vivo, accompanied by decreased inflammatory cytokines and increased osteogenic factor expression. Comprehensive transcriptomic and metabolomic analyses revealed the PPAR signaling pathway and associated lipid metabolism processes as critical targets during the LbGP-mediated periodontal bone remodeling. In vitro investigations further confirmed that LbGP induces metabolic reprogramming in macrophages by targeting the PPAR signaling pathway, thereby decreasing lipid droplet accumulation and inflammatory cytokine secretion via ACSL1 modulation without affecting fatty acid transport, ultimately facilitating bone regeneration. This work elucidates LbGP effectively modulates the osteoimmune microenvironment in periodontitis via macrophage reprogramming and ACSL1-mediated inhibition of PPAR signaling, suggesting a potential therapeutic strategy.