Berberine regulates MMPs/TIMP via inhibition of P38 MAPK/NF-κB phosphorylation and anti-inflammation in rat experimental periodontitis

Objective: To investigate the effects of berberine on matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases (MMPs/TIMPs) in rat periodontitis. Methods: Adult male Sprague-Dawley rats were subjected to thread ligation and porphyromonas gingivalis (P. gingivalis) inoculation resulting in periodontitis. Berberine [150 mg/(kg·d)] or vehicle was administered by oral gavage for 4 weeks. Alveolar bone loss and soft-tissue destruction were determined by micro-computed tomography (μ-CT) and HE staining. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) of gingival tissue were examined by ELISA. The expressions of MMP-2, MMP-9 and TIMP-2 as well as the phosphorylation of P38 MAPK and NF-κB were determined by Western blot. Results: Significant increases were observed in alveolar bone loss and periodontal soft-tissue destruction with higher levels of TNF-α, IL-1β and MMP-2/9 expressions and the activities of P38 MAPK and NF-κB in the experiment periodontitis group. Berberine of [150 mg/(kg·d)] not only improved the periodontal tissue and decreased alveolar bone loss, but also reduced the contents of TNF-α, IL-1β and MMP-2/9 and increased TIMP-2. In addition, berberine inhibited the phosphorylation of P38 MAPK/NF-κB. Conclusion: Berberine protects against periodontal tissue damage via decreasing MMP-2 and MMP-9 expressions but increasing TIMP-2 expression, which may be induced by inhibition of P38 MAPK/NF-κB and the anti-inflammatory effect on rat periodontitis.