Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption

• Published in: Biochemical pharmacology 2003, Vol.65 (1), p.35-42
• Main Authors: Wattel, Alice, Kamel, Said, Mentaverri, Romuald, Lorget, Florence, Prouillet, Christophe, Petit, Jean-Pierre, Fardelonne, Patrice, Brazier, Michel
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biological and medical sciences; Bone resorption; Bone Resorption - prevention & control; Bones, joints and connective tissue. Antiinflammatory agents; Flavonoids; Flavonoids - therapeutic use; Kaempferol; Kaempferols; Medical sciences; Models, Animal; Osteoclasts; Osteoclasts - cytology; Osteoclasts - drug effects; Pharmacology. Drug treatments; Quercetin; Quercetin - therapeutic use; Rabbits; Reactive Oxygen Species - metabolism
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(02)01445-4

Several recent studies have suggested that flavonols, a class of phytochemicals with many biological activities, might exert a protective effect against post-menopausal bone loss. In the present study, we investigated the effects of quercetin and kaempferol, two of the major naturally occurring flavonols on the in vitro bone resorbing activity of osteoclasts. Our results indicate that both compounds, at concentrations ranging from 0.1 to 100 μM reduce bone resorption in a time and dose-dependent manner. Significant inhibitory effects were observed at concentrations as low as 0.1 μM especially with kaempferol. The ic 50s, or concentration inhibitory of 50% of basal resorption, calculated for quercetin and kaempferol were 1.6 and 5.3 μM, respectively. Using highly purified rabbit osteoclasts, we showed that both flavonols directly induce apoptosis of mature osteoclasts in the same dose-range effective for inhibiting bone resorption. When osteoclasts were treated with 50 μM of quercetin and kaempferol, intracellular reactive oxygen species levels decreased significantly by 75 and 25%, respectively, indicating these molecules keep their antioxidant properties at this concentration. However, at concentrations below 50 μM, neither quercetin nor kaempferol exerted antiradical action, suggesting that antioxidant properties cannot fully explain the inhibitory effect on bone resorption. Finally, we report that kaempferol-, but not the quercetin-induced inhibition of bone resorption was partially abolished by the presence of the pure anti-estrogen ICI 182780 suggesting that kaempferol’s estrogenic effect could be involved in the inhibition of bone resorption. The present study demonstrates that flavonols widely distributed in human diet such as quercetin and kaempferol, exert a potent inhibitory effect on in vitro bone resorption.