Tetramethoxyluteolin, an active constituent in mulberry leaves, promotes osteogenesis of jaw bone marrow mesenchymal stem cells in periodontitis microenvironment via NF-κB inhibition.

Abstract

OBJECTIVE: This study aims to investigate the effects and mechanisms of tetramethoxyluteolin (TML), a bioactive compound in mulberry leaves, on jaw bone marrow mesenchymal stem cells (JBMMSCs) in a periodontitis microenvironment. DESIGN: Network pharmacology and molecular docking were used to identify mulberry leaves' active constituents and their targets in periodontitis treatment. An inflammatory model was established in JBMMSCs using Porphyromonas gingivalis-lipopolysaccharide (5 μg/mL). TML's optimal concentration was determined via CCK-8 and ELISA. Osteogenic differentiation, inflammatory markers, and NF-κB pathway activity were assessed using ALP/ARS staining, RT-PCR, and Western blot (WB). A rat model of ligature-induced periodontitis was established, and TML's effects were evaluated through histopathological staining, micro-CT, RT-PCR, and WB. JBMMSCs from each animal experimental group were isolated for in vitro osteogenic validation. Mechanisms were clarified by comparing TML with the NF-κB inhibitor BAY11-7082. RESULTS: TML was identified as the key constituent targeting NF-κB and inflammatory mediators (IL-6, IL-1β, TNF-α). 5 μM TML significantly suppressed inflammatory cytokines, promoted osteogenic differentiation, and inhibited NF-κB activation in JBMMSCs. In rats, 30 mg/kg TML markedly reduced inflammation and alveolar bone loss, showing efficacy comparable to indomethacin, and JBMMSCs from TML-treated groups exhibited enhanced osteogenesis. TML's inhibition of NF-κB was similar to BAY11-7082. CONCLUSION: TML reduces periodontal inflammation and enhances the osteogenic potential of JBMMSCs by inhibiting the NF-κB pathway, providing a novel strategy for periodontitis-related bone regeneration.