Actions of grape seed extract in rodent brain and differences in metabolism of its polyphenols in a rodent model of menopause.

摘要

Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control pups. These results suggest that the beneficial actions of GSE on learning and memory may be independent of enhancement of hippocampal neurogenesis. Lowered estrogen that accompanies menopause has been associated with impaired cognitive function in women. Ovariectomized (OVX) rats are used to model menopause and GSE enhanced cognition in young OVX rats. We hypothesized that GSE attenuates cognitive impairment in an older rodent model of menopause that more closely relates to human menopause. Rats were OVX at 6 months of age, given GSE for 6 months, and tested for cognitive function at 12 and 16 months of age. Unexpectedly, there was no measurable cognitive impairment due to OVX, nor was there a measurable effect of GSE on OVX or sham-OVX rats. 17beta-Estradiol, which is produced primarily in the ovaries, has been shown to reduce expression and activity of catechol-O-methyltransferase and uridine 5'-diphospho-glucuronosyltransferases. These enzymes are involved in the metabolism of catechin and epicatechin which, along with their metabolites, are thought to be the bioactive components of GSE. We hypothesized that OVX rats have increased methylated and/or glucuronidated forms of catechin and epicatechin. Urine from 18-week-old OVX rats given GSE for 4 days had increased glucuronidated catechin and epicatechin but no changes in methylated catechin and epicatechin compared to sham-OVX rats. These data are the first to show that in a rodent model of menopause a change in urinary catechin metabolites and suggest that postmenopausal women may experience increased metabolism of catechin containing dietary supplements.