The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No.
4 • September 2003
Quercetin and Kaempferol Inhibit in Vitro Osteoclastic Bone Resorption
As noted above, quercetin and kaempferol are flavonoids that inhibit xanthine oxidase, which is associated with cytokine-induced osteoclastic bone resorption. A recent paper examined the effects of quercetin and kaempferol on in vitro osteoclastic bone resorption and found both not only to inhibit bone resorption, but also to directly induce apoptosis of mature osteoclasts in the same dose range. When osteoclasts were treated with 50-µM quercetin and kaempferol, intracellular reactive oxygen species levels decreased significantly, by 75% and 25%, and apoptotic osteoclasts in cultures were increased about 3-fold compared with control cultures. At concentrations below 50 µM, however, neither flavonoid had antiradical action, suggesting, the authors say, that antioxidant properties cannot fully explain the inhibitory effect on bone resorption, because at lower doses (0.1 µM, 1 µM, and 10 µM), the flavonoids had pro-oxidant effects (particularly for kaempferol) and still had apoptotic effects on the osteoclasts in culture.
The authors show here that quercetin and kaempferol directly promoted spontaneous apoptosis of osteoclasts in a dose range that correlated well with those for inhibition of bone resorption. Kaempferol was observed to stimulate apoptosis at lower concentrations (0.1 µM and 1 µM) than quercetin (where effects were first noted at 10 µM), but quercetin effects were observed earlier.
The researchers examined whether estrogenic effects of the flavonoids were part of their anti-bone-resorption effects. They used ICI 182780, a pure antagonist that can block the estrogen receptor, and found that it partially reversed the inhibitory effect on resorption by kaempferol, but not by quercetin. Estrogens and bisphosphonates (a class of drug used to treat bone loss) act at least in part by inducing osteoclast apoptosis.
The authors also report a study that showed that several vegetables, especially onion extracts (a relatively rich source of quercetin), can significantly inhibit bone resorption in the rat. Another recent study reported that, among elderly women in Britain, tea (another source of quercetin) drinkers had significantly greater bone mineral density than non-tea drinkers. The authors note that possible candidates as bioactive molecules in onion and tea are flavonols. A further study found that rutin, a quercetin glycoside, can preserve bone mass in ovariectomized rats by slowing down bone resorption.
- Wattel et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol 65:35-42 (2003).