Antagonistic effects of extract from leaves of Ginkgo biloba on glutamate neurotoxicity.
Zhu L Wu J Liao H Gao J Zhao XN Zhang ZX
Acta Pharmacol Sin 1997 JUL;18(4):344
Zhu L, Nanjing Univ, Sch Med, Nanjing 210093, PEOPLES R CHINA
AIM: To determine whether the extract of leaves of Ginkgo biloba L (EGb) and several active constituents of EGb have protective effects against glutamate (Glu)-induced neuronal damage. METHODS: Microscopy and image analysis of nucleus areas in the arcuate nuclei (AN) of mice were made. The neuronal viability in primary cultures from mouse cerebral cortex was assessed using MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] staining and the intracellular free calcium concentration ([Ca2+](i)) of single neuron was measured using Fura-2. RESULTS: EGb (2.5 mg.L-1) and its constituent ginkgolide B (Gin B, 2 mg.L-1) protected the neuronal viability against Glu-induced injury, and prevented the Glu-induced elevation in [Ca2+](i). EGb (3 - 10 mg.kg(-1)) attenuated the decrease of nucleus areas in arcuate nuclei induced by Glu (1 g.kg(-1), sc). CONCLUSION: EGb and Gin B prevent neurons from Glu neurotoxicity through reduction of the rise in [Ca2+](i).
Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats.
Jastreboff PJ Zhou ST Jastreboff MM Kwapisz U Gryczynska U
Audiol Neuro Otol 1997 JUL-AUG;2(4):197-212
Jastreboff PJ, Univ Maryland, Sch Med, Dept Surg, Tinnitus & Hyperacusis Ctr, 10 S Pine St, Mstf Bldg, RM 436, Baltimore,MD 21201 USA
The effects of an extract from Ginkgo biloba, EGb 761, on tinnitus were tested using an animal model of tinnitus. Daily oral administration of EGb 761 in doses from 10 to 100 mg/kg/day began 2 weeks before behavioral procedures and continued until the end of the experiment. Tinnitus was induced by daily administration of 321 mg/kg sodium salicylate s.c. (corresponding to 275 mg/kg/day of salicylate acid) in fourteen groups of pigmented rats, 6 animals/group. The results from salicylate- and EGb-76 1- treated animals were compared to control groups receiving either salicylate, saline, or EGb 761 only in doses of 100 mg/kg. Administration of EGb 761 resulted in a statistically significant decrease of the behavioral manifestation of tinnitus for doses of 25, 50 and 100 mg/kg/day.
Phospholipid breakdown and choline release under hypoxic conditions: Inhibition by bilobalide, a constituent of Ginkgo biloba.
Klein J Chatterjee SS Loffelholz K
Brain Res 1997 MAY 2;755(2):347-350
Klein J, Univ Mainz, Dept Pharmacol, Obere Zahlbacher Str 67, D 55101 Mainz, GERMANY
A marked increase of choline release from rat hippocampal slices was observed when the slices were superfused with oxygen-free buffer, indicating hypoxia-induced hydrolysis of choline-containing phospholipids. This increase of choline release was suppressed by bilohalide, an ingredient of Ginkgo biloba, but not by a mixture of ginkgolides. The EC50 value for bilobalide was 0.38 mu M. In ex vivo experiments, bilobalide also inhibited hypoxia- induced choline release when given p.o. In doses of 2-20 mg/kg 1 h prior to slice preparation. The half-maximum effect was observed with 6 mg/kg bilobalide. A similar effect was noted after p.o. Administration of 200 mg/kg EGb 761, a ginkgo extract containing approximately 3% of bilobalide. We conclude that gi nkgo extracts can suppress hypoxia-induced membrane breakdown in the brain, and that bilobalide is the active constituent for this effect.
Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi- infarct dementia (Reprinted f rom Pharmacopsychiat, vol 29, pg 47-56, 1996).
Kanowski S Herrmann WM Stephan K Wierich W Horr R
Phytomedicine 1997 MAR;4(1):3-13
Kanowski S, Free Univ Berlin, Klinikum Benjamin Franklin, ABT Gerontopsychiat, Dept Gerontopsychiat, D 14050 Berlin, GERMANY
The efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study After a 4-week run- in period, 216 patients were included in the randomized 24- week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT)(1) for the assessment of the patient's attention and memory, and the Nurnberger Alters-Beobachtungsskala (NAB)(2) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p 0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.
Effect of Ginkgo biloba extract (EGb 761) on the vasospastic response of mouse cutaneous arterioles to platelet activation.
Stucker O Pons C Duverger JP Drieu K DArbigny P
Int J Microcirc Clin Exp 1997 MAR-APR;17(2):61-66
Stucker O, Cerom, 155 Rue Faubourg St Denis, F 75010 Paris, FRANCE
The effect of intravenously administered Ginkbo biloba extract (EGb 761) on the vasospastic response to platelet activation has been assessed using a cutaneous flap preparation in anaesthetized mice. Arterioles of the axillary artery were observed by intravital microscopy, and platelets were activated by topical application of ADP under two steady state conditions: normothermia (37 degrees C) and hypothermia (24 degrees C). Responses of the cutaneous arterioles to stimulation by topical application of a thromboxane agonist (U46619) were also compared in animals treated intravenously with EGb 761 or with a thromboxane synthesis inhibitor (U63557). ADP induced a 34% constriction of the arterioles in control animals. However, no arteriolar constriction occurred in response to ADP in platelet-depleted animals (collagen- induced thrombocytopenia) or in animals treated with EGb 761 (60 mg/kg, i.v.). Exposure of the arterioles to hypothermia (24 degrees C) for 10 min induced constriction of 7-12% in all experimental groups of animals. Under these hypothermic conditions, either EGb 761 or thrombocytopenia abolished ADP-induced arteriolar constriction which was substituted by arteriolar dilation, indicating that EGb 761 can inhibit tile vasospasm that is produced by platelet activation. As topically applied U46619 (10(-5) M) induced arterioles constriction (about 22%) that was abolished by intravenous treatment with EGb 761, the extract appears to act directly rather than as a thromboxane synthase inhibitor. Collectively, these findings indicate that platelet factors can play a significant role in cutaneous vasospasm, and that EGb 761, via an action on the thromboxane pathway, could be useful in treating Raynaud's phenomenon and other vascular disorders which involve increased thromboxane production.