Combined Effects of Puerarin and Adipose-Derived Stem Cells on Alveolar Bone Preservation and Inflammation Control in Periodontitis Through p38MAPK Modulation

This study evaluated the effects of puerarin and adipose-derived stem cells (ADSCs), alone or combined, on p38MAPK activity, alveolar bone preservation, and inflammatory responses in a rat periodontitis (PD) model and in vitro. ADSCs were exposed to various puerarin concentrations to assess cell proliferation, osteogenic differentiation, and p38MAPK-related protein expression. Additional experiments employed anisomycin (a p38 MAPK Activator) and Porphyromonas gingivalis LPS (Pg-LPS) to determine whether puerarin attenuates p38MAPK overactivation and reduces pro-inflammatory cytokine production. In vivo, ligature- and Porphyromonas gingivalis-induced periodontitis rats were randomized to Normal, PD, PD + ADSCs, PD + puerarin, or PD + puerarin + ADSCs groups, and alveolar bone microarchitecture (micro-CT) and periodontal p38MAPK activation and osteogenic/inflammatory proteins (Western blot, ELISA) were assessed. At 10^-6 M, puerarin significantly increased ADSC proliferation and osteogenic differentiation, whereas anisomycin activation diminished these benefits, which were restored by co-treatment with puerarin. Puerarin also reduced Pg-LPS induced secretion of pro-inflammatory cytokines by suppressing p38MAPK. In vivo, the periodontitis group showed substantial alveolar bone loss and marked inflammatory cell infiltration. Both ADSCs and puerarin partially alleviated these changes but did not fully reverse them. Notably, their combination provided the greatest benefit, nearly normalizing alveolar bone parameters, strongly inhibiting p38MAPK, and further reducing inflammatory cytokine levels in periodontal tissues. Collectively, puerarin and ADSCs exert complementary anti-inflammatory and pro-osteogenic effects associated with attenuation of p38MAPK signaling. Co-administration produced superior therapeutic outcomes, supporting this dual approach as a potential strategy for periodontitis-associated bone loss.