The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba

doi:10.1073/pnas.111126298

The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba

^*Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; ^†Institute of Animal Nutrition, Physiology, and Metabolism, Christian-Albrechts-University, 24118 Kiel, Germany; ^‡School of Food Biosciences, Hugh Sinclair Human Nutrition Unit, University of Reading, Reading RG6 6AP, United Kingdom; ^§School of Pharmacy, University of Southern California, Los Angeles, CA 90033; ^¶Environmental Energy Technologies Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; and ^**Department of Internal Medicine, University of California, Davis, CA 95616-8587

Contributed by Peter G. Schultz

Abstract

Extracts of Ginkgo biloba leaves are consumed as dietary supplements to counteract chronic, age-related neurological disorders. We have applied high-density oligonucleotide microarrays to define the transcriptional effects in the cortex and hippocampus of mice whose diets were supplemented with the herbal extract. Gene expression analysis focused on the mRNAs that showed a more than 3-fold change in their expression. In the cortex, mRNAs for neuronal tyrosine/threonine phosphatase 1, and microtubule-associated τ were significantly enhanced. Hyperphosphorylated τ is the major constituent of the neurofibrillary tangles in the brains of Alzheimer's disease patients. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-2, calcium and chloride channels, prolactin, and growth hormone (GH), all of which are associated with brain function, were also up-regulated. In the hippocampus, only transthyretin mRNA was upregulated. Transthyretin plays a role in hormone transport in the brain and possibly a neuroprotective role by amyloid-β sequestration. This study reveals that diets supplemented with Ginkgo biloba extract have notable neuromodulatory effects in vivo and illustrates the utility of genome-wide expression monitoring to investigate the biological actions of complex extracts.

Footnotes

↵ ‖ To whom reprint requests should be addressed. E-mail: schultz{at}gnf.org.
Abbreviations:

AMPA,

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;

EST,

expressed sequence tag;

RT-PCR,

reverse transcription–PCR;

GH,

growth hormone