Anti-inflammatory, anti-osteoclastic, and antioxidant activities of genistein protect against alveolar bone loss and periodontal tissue degradation in a mouse model of periodontitis.

Genistein, a dietary polyphenol primarily found in soy products, has beneficial effects on bone. However, the effect of genistein on inflammatory periodontal destruction has not been investigated in detail. We explored whether genistein protects against lipopolysaccharide (LPS)/ligature-induced periodontitis in mice. We also examined the effect of genistein on LPS-stimulated inflammatory and oxidative stress using RAW 264.7 macrophages and human gingival fibroblasts (hGFs). The results from μCT and histological analyses revealed that intraperitoneal injection of genistein (20 mg/kg body weight) daily for three weeks inhibited LPS-mediated alveolar bone loss and periodontal tissue degradation. The administration of genistein also inhibited osteoclast formation and the expression of inflammation-related molecules in the inflamed region of mice with periodontitis. Treatment with 30-70 μM genistein significantly prevented osteoclast differentiation in receptor activator of nuclear factor κB ligand- or LPS-stimulated macrophages by suppressing the expression of osteoclast-specific molecules. The addition of genistein led to a dose-dependent inhibition of the expression of inflammation-related molecules both in LPS-stimulated macrophages and hGFs. In addition, genistein at 50 μM protected hGFs from LPS-mediated stresses such as mitochondrial impairment and cellular ROS accumulation. However, such protection was significantly diminished by combined treatment with 25 nM bafilomycin A1, a chemical autophagy inhibitor. Collectively, our results indicate that genistein protects against inflammatory periodontal damage by regulating autophagy induction and inhibiting osteoclast activation, the production of inflammation mediators, and mitochondrial oxidative damage.