Estrogenic Activity

For a number of years, conclusions from epidemiological evidence indicated that estrogen-replacement therapy (estrogen-replacement therapy) had a preventative role against Alzheimer’s disease development, and estrogen treatment in women with Alzheimer’s disease enhanced cognitive function. The mechanisms by which estrogens may protect against Alzheimer’s disease are unclear but may be mediated via interaction with estrogen receptors in the CNS, or perhaps by effects on neurotransmitter systems, modulation of NGF, enhancement of cerebral blood flow or antioxidant effects or other unknown mechanisms. However, evidence from some more recent studies does not support an association between high estrogen levels and a reduced incidence of Alzheimer’s disease. Nevertheless, the estrogenic activities of some plant extracts have been explored as one possible explanation for their reputed memory-enhancing effects.

Soya beans, the seeds of Glycine max Merr. (Leguminosae), form an important part of the traditional diet in China and other parts of the Far East and are frequently a staple of the diet of vegetarians and vegans. Soya contains isoflavones including genistein and daidzein, which have been characterised as phytoestrogens. Some studies indicate that phytoestrogens may alter anxiety, learning and memory in vivo. Phytoestrogens, particularly the soya isoflavones, are reported to improve cognitive function, not only in some animal studies but also in some clinical studies, and have been suggested to offer protection against Alzheimer’s disease development. One study in student volunteers suggested that a high soya diet (100 mg total isoflavones/d for 10 weeks) may improve short- and long-term memory in both females and males. Another study showed that consumption of soya isoflavones by postmenopausal women for a period of 12 weeks improved cognitive function. In a double-blind, randomised, placebo-controlled trial, some cognitive benefits, particularly verbal memory, occurred in postmenopausal women taking isoflavone supplements for 6 months.

The mode of action of phytoestrogens to explain favourable effects on cognition is unclear, and they may act similarly to estrogen-replacement therapy and via interaction with the estrogen receptor or by other mechanisms, perhaps independently of the estrogen receptor. For example, genistein showed a neuroprotective effect against beta-amyloid-induced neurotoxicity in vitro, and it ameliorated β-amyloid peptide-induced hippocampal neuronal apoptosis in vitro, which could be associated with an antioxi-dant effect. It has been proposed that although phytoestrogens may exert some neuroprotective effects analogous to that of antioxidants, they are not functionally equivalent to the endogenously active estrogens.

Many other plants have been considered to display estrogenic effects in some studies, but their physiological significance and any potential clinical relevance in improving cognition require further investigation. Pueraria lobata (Willd.) Ohwi (Leguminosae), a plant used in traditional Chinese medicine (TCM), and some of its component isoflavones (e.g. puerarin) have shown estrogenic activity in vitro. Puerarin also attenuates the deficits of inhibitory avoidance performance in rats, which was associated with an increase in cholinergic activity via nico-tinic, but not muscarinic, receptors, in addition to activation of N-methyl-D-aspartate (NMDA) receptors, and a decrease in serotonergic neuronal activity. Another study in which postmenopausal women were treated with P. lobata (equivalent to 100 mg isoflavones) for 3 months suggested it could promote some favourable effects on cognitive function. It is apparent that some phytoestrogens do show potential for use in some cognitive-related disorders, but more extensive and longer-term studies are needed.