IN-VIVO REGULATION OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR AND GLUCOCORTICOID SYNTHESIS BY GINKGO-BILOBA EXTRACT EGB-761 AND ISOLATED GINKGOLIDES

Glucocorticoid excess has broad pathogenic potential including neuroto xicity, neuroendangerment, and immunosuppression. Glucocorticoid synth esis is regulated by ACTH, which acts by accelerating the transport of the precursor cholesterol to the mitochondria where steroidogenesis b egins. Ginkgo biloba is one of the most ancient trees, and extracts fr om its leaves have been used in traditional medicine. A standardized e xtract of Ginkgo biloba leaves, termed EGb 761 (EGb), has been shown t o have neuroprotective and antistress effects. In vivo treatment of ra ts with EGb, and its bioactive components ginkgolide A and B, specific ally reduces the ligand binding capacity, protein, and messenger RNA e xpression of the adrenocortical mitochondrial peripheral-type benzodia zepine receptor (PER), a key element in the regulation of cholesterol transport, resulting in decreased corticosteroid synthesis. As expecte d, the ginkgolide-induced decrease in glucocorticoid levels resulted i n increased ACTH release, which in turn induced the expression of the steroidogenic acute regulatory protein. Because ginkgolides reduced th e adrenal PER expression and corticosterone synthesis despite the pres ence of high levels of steroidogenic acute regulatory protein, these d ata demonstrate that PER is indispensable for normal adrenal function. In addition, these results suggest that manipulation of PER expressio n could control circulating glucocorticoid levels, and that the antist ress and neuroprotective effects of EGb are caused by to its effect on glucocorticoid biosynthesis.