The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No. 3 • June 2003

Phytoestrogens: Neuroprotective Properties Independent of Estrogenic Effects

A fairly recent paper1 found no correlation between the cytoprotective (cell-protective) effects and estrogenic potency of various natural and synthetic mono- and polyphenolic compounds in cultures of mouse hippocampal HT22 cells and human SK-N-MC neuroblastoma cells. The authors studied the neuroprotective effects of molecules that lack estrogenic hormonal effects but are equally effective neuroprotective antioxidants compared with 17-beta-estradiol, the natural human female sex hormone. Major phytoestrogens (that do have some estrogenic effects) include some of the flavonoids, such as quercetin (found in onions) and catechins (found in tea), and the stilbenes, such as resveratrol (found in grapes and wine). There are also xenobiotic estrogenlike substances, such as bisphenol A (a plastic-material monomer), certain polymer plasticizers, and detergent-related chemicals.

One way the scientists tested the correlation between neuroprotection and estrogenic activity was to measure the antioxidative neuroprotective effect of the phenolic compounds while adding an antiestrogen (ICI 182780) to the cell medium. Thus, while the phenolic compounds have varying degrees of estrogenic activity, this experiment found that blocking the estrogenic activity did not interfere with the neuroprotective effects. In fact, the neuroprotective activities of 17-beta-estradiol, the natural female sex hormone, was not diminished by the concomitant administration of high doses of antiestrogens! A neuroprotective effect against glutamate toxicity was found in the HT22 cells exposed to the phenols serotonin, N-acetylserotonin, resveratrol, quercetin, or 4-dodecylphenol. This is extremely interesting because there are many phytoestrogens that are thought to mimic estrogen in the latter’s neuroprotective effects, yet these protective effects may actually be independent of the phytoestrogens’ estrogenic effects and depend, instead, on their phenolic structure.

  1. Moosmann and Behl. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci USA 96:8867-72 (1999).

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