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全球基因表达分析确定了银杏叶提取物EGb 761的细胞和组织特异性作用。

Global gene expression analysis identifies cell and tissue specific actions of Ginkgo biloba extract, EGb 761.

作者信息

Gohil Kishorchandra, Packer Lester

机构信息

University of California, Davis 95616, USA.

出版信息

Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):625-31.

Abstract

Clinical and pre-clinical uses of Ginkgo biloba extract encompass a broad spectrum of pathologies that include peripheral arterial disorders, cardiovascular and neuronal dysfunctions and resolution of ischemia-reperfusion injuries. Many of these pathologies develop over time and recruit multiple cell types and molecular pathways that alter the cellular a nd molecular profiles of the failing targetorgans. Transcriptional processes are important determinants of the pathogenesis of these chronic disease states. Therefore the potential therapeutic and preventive actions of a standardized Ginkgo biloba extract, EGb 761, may be affected through modulation of transcriptional processes. We have used various techniques for large-scale mRNA expression analysis, including differential display of mRNAs, cDNA arrays and high-density oligonucleotide arrays, to evaluate the actions of EGb 761 on the activities of the genomes in vitro and in vivo. The results show broad but cell specific actions of Ginkgo biloba extract that may enhance antioxidant defenses in vitro in cancer cells and modulate neuronal functions in cortex and hippocampus in brain in vivo. The large scale analysis of mRNAs in response to Ginkgo biloba extract in vitro and in vivo show that the standardized extract affects the activities of the mammalian genome. The data provide some support for the concept that the actions of EGb 761 are mediated through it effects on the process of gene transcription which plays a causative role in chronic diseases.

摘要

银杏叶提取物的临床和临床前应用涵盖了广泛的病理状况,包括外周动脉疾病、心血管和神经功能障碍以及缺血再灌注损伤的缓解。这些病理状况中的许多是随着时间发展的,涉及多种细胞类型和分子途径,从而改变了功能衰竭靶器官的细胞和分子特征。转录过程是这些慢性疾病发病机制的重要决定因素。因此,标准化银杏叶提取物EGb 761的潜在治疗和预防作用可能通过调节转录过程而受到影响。我们使用了各种大规模mRNA表达分析技术,包括mRNA差异显示、cDNA阵列和高密度寡核苷酸阵列,来评估EGb 761在体外和体内对基因组活性的作用。结果表明,银杏叶提取物具有广泛但细胞特异性的作用,它可能在体外增强癌细胞的抗氧化防御能力,并在体内调节大脑皮层和海马体中的神经功能。对体外和体内响应银杏叶提取物的mRNA进行的大规模分析表明,标准化提取物会影响哺乳动物基因组的活性。这些数据为EGb 761的作用是通过其对基因转录过程的影响介导的这一概念提供了一些支持,而基因转录过程在慢性疾病中起着致病作用。

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