Effects of Ginkgo biloba extract (EGb 761) on gene expression:: Possible relevance to neurological disorders and age-associated cognitive impairment

Ginkgo biloba leaf extract (EGb 761), which contains many constituents, including flavonoid glycosides and terpenoids (ginkgolides, bilobalide), is used to treat cerebrovascular and peripheral vascular insufficiency, as well as cognitive impairment and other symptoms of dementia. Recent studies have indicated that these therapeutic effects of EGb 761 probably involve modification of the expression of many genes by actions involving several of its active constituents. As examples: EGb 761 and its ginkgolide B constituent inhibit the expression of the peripheral benzodiazepine receptor in the adrenal cortex and decrease circulating levels of corticosterone in the rat, effects that provide a mechanism for explaining the "antistress" action of the extract. Both the flavonoid and terpenoid constituents of EGb 761 decrease the expression of inducible nitric oxide synthase (iNOS), supporting an action of the extract of opposing the deleterious effects of excessive formation of NO. EGb 761 upregulates several genes that encode vital antioxidant enzymes, including heme oxygenase-1 and the regulatory and catalytic subunits of gamma-glutamyl-cysteinyl synthetase. Dietary treatment of mice with EGb 761 upregulates the expression of genes encoding neuronal tyrosine/threonine phosphatase I and microtubule-associated tau in the cerebral cortex, findings that are of interest since these proteins are associated with the intracellular neurofibrillary tangles found in the brain in Alzheimer's disease. Bilobalide upregulates two mitochondrial-DNA-encoded genes, subunit III of cytochrome c oxidase and subunit ND1 of NADH dehydrogenase, indicating a fundamental mechanism that may underlie EGb 761-induced neuroprotection. Collectively, such results indicate that the therapeutic effects of EGb 761 on cognitive impairment (dementia) may involve its action of altering gene expression. (C) 2003 Wiley-Liss, Inc.