Watanabe C M, Wolffram S, Ader P, Rimbach G, Packer L, Maguire J J, Schultz P G, Gohil K
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6577-80. doi: 10.1073/pnas.111126298. Epub 2001 May 29.
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 tau were significantly enhanced. Hyperphosphorylated tau is the major constituent of the neurofibrillary tangles in the brains of Alzheimer's disease patients. The expression of alpha-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-beta 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.
银杏叶提取物作为膳食补充剂用于对抗慢性、与年龄相关的神经紊乱。我们应用高密度寡核苷酸微阵列来确定饮食中添加了这种草药提取物的小鼠的大脑皮层和海马体中的转录效应。基因表达分析聚焦于那些表达变化超过3倍的mRNA。在大脑皮层中,神经元酪氨酸/苏氨酸磷酸酶1和微管相关tau蛋白的mRNA显著增加。过度磷酸化的tau蛋白是阿尔茨海默病患者大脑神经纤维缠结的主要成分。与脑功能相关的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)-2、钙通道、氯通道、催乳素和生长激素(GH)的表达也上调。在海马体中,只有转甲状腺素mRNA上调。转甲状腺素在大脑中激素运输中起作用,并且可能通过螯合β-淀粉样蛋白起到神经保护作用。这项研究表明,添加银杏叶提取物的饮食在体内具有显著的神经调节作用,并说明了全基因组表达监测在研究复杂提取物生物学作用方面的实用性。