In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides
In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides
复制标题
DOI：
10.1210/en.137.12.5707
复制
发表时间：
1996-12-01
期刊：
影响因子：
4.8
通讯作者：
Papadopoulos, V
中科院分区：
文献类型：
--
作者：
Amri, H;Ogwuegbu, SO;Papadopoulos, V
糖皮质激素过量具有广泛的致病潜力，包括神经毒性、神经危害和免疫抑制。糖皮质激素的合成受促肾上腺皮质激素的调节，促肾上腺皮质激素通过加速胆固醇前体向线粒体的转运而起作用，线粒体是类固醇生成的开始。银杏是最古老的树木之一，其叶的提取物已被用于传统医学。银杏叶的标准化提取物，称为EGb 761（EGb），已被证明具有神经保护和抗应激作用。在大鼠体内给予EGB及其生物活性成分银杏内酯A和B，可特异性降低肾上腺皮质线粒体外周型苯二氮受体（PER）的配体结合能力、蛋白质和信使RNA表达，PER是调节胆固醇转运的关键因素，导致皮质类固醇合成减少。正如预期的那样，银杏内酯诱导的糖皮质激素水平降低导致ACTH释放增加，这反过来又诱导了类固醇生成急性调节蛋白的表达。由于银杏内酯降低肾上腺PER表达和皮质酮合成，尽管存在高水平的类固醇生成急性调节蛋白，这些数据表明，PER是必不可少的正常肾上腺功能。此外，这些结果表明，PER表达的操纵可以控制循环糖皮质激素水平，并EGb的抗应激和神经保护作用是由其对糖皮质激素的生物合成的影响。
Glucocorticoid excess has broad pathogenic potential including neurotoxicity, neuroendangerment, and immunosuppression. Glucocorticoid synthesis is regulated by ACTH, which acts by accelerating the transport of the precursor cholesterol to the mitochondria where steroidogenesis begins. Ginkgo biloba is one of the most ancient trees, and extracts from its leaves have been used in traditional medicine. A standardized extract of Ginkgo biloba leaves, termed EGb 761 (EGb), has been shown to have neuroprotective and antistress effects. In vivo treatment of rats with EGb, and its bioactive components ginkgolide A and B, specifically reduces the ligand binding capacity, protein, and messenger RNA expression of the adrenocortical mitochondrial peripheral-type benzodiazepine receptor (PER), a key element in the regulation of cholesterol transport, resulting in decreased corticosteroid synthesis. As expected, the ginkgolide-induced decrease in glucocorticoid levels resulted in increased ACTH release, which in turn induced the expression of the steroidogenic acute regulatory protein. Because ginkgolides reduced the adrenal PER expression and corticosterone synthesis despite the presence of high levels of steroidogenic acute regulatory protein, these data demonstrate that PER is indispensable for normal adrenal function. In addition, these results suggest that manipulation of PER expression could control circulating glucocorticoid levels, and that the antistress and neuroprotective effects of EGb are caused by to its effect on glucocorticoid biosynthesis.