Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans

Astrid Gutierrez-Zepeda
Ross Santell
Zhixin Wu
Marishka Brown
Yanjue Wu
Ikhlas Khan
Christopher D. Link
Baolu Zhao
Yuan Luo

Abstract

Background: Epidemiological studies have associated estrogen replacement therapy with a lower risk of developing Alzheimer's disease, but a higher risk of developing breast cancer and certain cardiovascular disorders. The neuroprotective effect of estrogen prompted us to determine potential therapeutic impact of soy-derived estrogenic compounds. Transgenic C. elegans, that express human beta amyloid (A beta), were fed with soy derived isoflavones genistein, daidzein and glycitein ( 100 mu g/ml) and then examined for A beta-induced paralysis and the levels of reactive oxygen species. Results: Among the three compounds tested, only glycitein alleviated A beta expression- induced paralysis in the transgenic C. elegans. This activity of glycitein correlated with a reduced level of hydrogen peroxide in the transgenic C. elegans. In vitro scavenging effects of glycitein on three types of reactive oxygen species confirmed its antioxidant properties. Furthermore, the transgenic C. elegans fed with glycitein exhibited reduced formation of beta amyloid. Conclusion: These findings suggest that a specific soy isoflavone glycitein may suppress A beta toxicity through combined antioxidative activity and inhibition of A beta deposition, thus may have therapeutic potential for prevention of A beta associated neurodegenerative disorders.