In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides.

Abstract

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 (PBR), 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 PBR expression and corticosterone synthesis despite the presence of high levels of steroidogenic acute regulatory protein, these data demonstrate that PBR is indispensable for normal adrenal function. In addition, these results suggest that manipulation of PBR expression could control circulating glucocorticoid levels, and that the antistress and neuroprotective effects of EGb are caused by to its effect on glucocorticoid biosynthesis.

Preventive Effect of Ginkgo biloba Extract (GBB) on the Lipopolysaccharide-Induced Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 via Suppression of Nuclear Factor-.KAPPA.B in RAW 264.7 Cells

“…[29][30][31] The cellular mechanisms underlying these multiple effects can be attributed to different components in the extract, which may act independently or synergistically. Although some of the cellular mechanisms have been found to involve terpenes such as ginkgolides or bilobalide, 32,33) many remain unexplained, despite the large number of experiments performed on these materials. Moreover, the anti-inflammatory effects of the water soluble portion of EGb 761 on inflammation caused by Candida albicans revealed that the terpene, rather than the flavone portion of this material is responsible for these therapeutic effects.…”

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

“…Rats were sacrificed 24 h later. Corticosterone was measured in organic extracts (ethyl acetate/ether, 1:1, v/v) of the collected sera by radioimmunoassay (Amri et al, 1996) under conditions suggested by the supplier of the antisera, ICN Diagnostics Division (Orangeburg, NY).…”

“…MA-10 mouse Leydig tumor cells were cultured in DMEM/F-12 medium supplemented with 5% FBS and 2.5% horse serum under 4% CO 2 (Brown et al, 1992). Human adrenal tumor H295R cells were maintained in DMEM/F-12 with 1% ITS ϩ [insulin (1 g/ml), transferrin (1 g/ml), selenium (1 g/ml), linoleic acid (1 g/ml), and bovine serum albumin (1.25 mg/ml)], 2.5% Nuserum, and 1% penicillin-streptomycin at 37°C, 6% CO 2 (Amri et al, 1996). Hepa1-6 mouse hepatoma cells were cultured in DMEM supplemented with 10% FBS and UT-1 cells were cultured in DMEM/F-12 medium supplemented with 8% fetal bovine lipoprotein-deficient serum and 2% FBS plus 40 M Compactin (Chin et al, 1982).…”

“…H295R human adrenal tumor cells were seeded in 48-well plates at 10 5 cells/well and incubated for 24 h. After removal of culture media, cells were incubated in the presence of procaine (0.1, 1, 10, and 100 M) or Anticort (0.1, 1, 10, and 100 M jpet.aspetjournals.org based on procaine content) for another 48-h period. At the end of the incubation time period cells were treated with or without 1 mM dbcAMP for 48 h. Cortisol levels in the media were determined by radioimmunoassay as previously described (Amri et al, 1996).…”

Improvement In Rabbit Corneal Cell Suspension Viability After Freezing With Gingko Biloba Extrakt

“…One component in EGb 761 is that the flavonoids have protective effects on cell membranes against destructive effects of free radicals and lipid peroxidation (2). Another important group found in EGb 761, the terpenoids, exhibit significant antioxidant activity (8) and regulate some mitochondria enzyme properties (1). The number of components in EGb 761 is over 60.…”