Phytoestrogen kaempferol (3,4',5,7-tetrahydroxyflavone) protects PC12 and T47D cells from beta-amyloid-induced toxicity.
In clinical studies, it has been shown that estrogen replacement therapy in menopause is strongly correlated with a reduced risk of the development of Alzheimer's disease (AD). In in vitro experiments, it was demonstrated that estradiol protects cells against the toxic effects of beta-amyloid, the major component of plaques in brains of AD patients. Therefore, estrogens have become interesting candidates for a possible treatment of neurodegeneration. In plants, a class of compounds has been identified that bind to human estrogen receptor, so-called phytoestrogens, which are part of our daily diet. Here, we compared the effects of alpha- and beta-estradiol with plant-derived kaempferol on beta-amyloid peptide-induced toxicity in PC12 neuroblastoma and T47D human breast cancer cells. The present results demonstrate a protective effect of kaempferol comparable to that observed with estradiol. The effects of the weak estrogen receptor agonists alpha-estradiol and kaempferol were found to be similar to the effects of the strong estrogen receptor agonist beta-estradiol, suggesting a mode of action independent from the nuclear estrogen receptor.
F. Hoffmann-LaRoche Ltd, Pharma Research Preclinical, Basel, Switzerland.
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Roth
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Schaffner
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Hertel
D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000494:pharmacology; D005419:Flavonoids; D006801:Humans; D044949:Kaempferols; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D005419:Flavonoids; D044949:Kaempferols; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D004958:Estradiol; C006552:kaempferol; D011794:Quercetin; D007770:L-Lactate Dehydrogenase