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Berberine had a clear inhibitory effect on alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis, and its putative mechanism of action was attributed to the downregulation of the activity of the P38MAPK/NF-κB pathway, mediated by the G Protein-coupled estrogen receptor. Berberine had a clear inhibitory effect on alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis, and its putative mechanism of action was attributed to the downregulation of the activity of the P38MAPK/NF-κB