Baicalin Alleviates LPS-Induced Apoptosis of Periodontal Ligament Cells Via Inhibiting Endoplasmic Reticulum Stress

This study aimed to investigate the effect of baicalin (BA) on Porphyromonas gingivalis lipopolysaccharide (Pg-LPS)-induced apoptosis in human periodontal ligament cells (hPDLCs) and to explore its underlying mechanisms using a periodontitis mouse model.

In vitro, the effects of BA on proliferation, apoptosis, and ER stress in Pg-LPS-induced hPDLCs were assessed using CCK-8, immunofluorescence staining, flow cytometry and Western blot. Molecular docking and molecular dynamics (MD) simulations were first conducted to predict the interaction between BA and PERK. The involvement of the PERK pathway was subsequently examined using the activator CCT020312 (CCT) and the inhibitor GSK2606414 (GSK). In vivo, a ligature-induced mouse periodontitis model was established to evaluate BA's therapeutic effects on periodontal tissue.

BA promoted hPDLCs proliferation and inhibited apoptosis by regulating BAX, Cleaved-Caspase3, and Bcl-2 expression. It reduced ER stress by decreasing the expression of GRP78 and PERK, with no significant effect on the expression of IRE1α and ATF6. Consistently, docking and MD simulations supported a stable interaction between BA and PERK (Glide gscore -7.98; stable RMSD). Furthermore, BA suppressed the PERK/eIF2α/ATF4/CHOP pathway, with GSK enhancing its protective effects. In vivo, BA reduced alveolar bone resorption and apoptosis in periodontitis mice, with the BA-GSK combination providing the strongest protection.

BA shows therapeutic potential for periodontitis by inhibiting ER stress - mediated apoptosis and protecting periodontal tissue.