Ginkgo Biloba Abstracts
GINKGO BILOBA RESEARCH SUMMARY
(REFERENCE 1 OF 24)
Rapin JR Lamproglou I Drieu K DeFeudis FV
Demonstration of the "anti-stress" activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task.
In: Gen Pharmacol (1994 Sep) 25(5):1009-16
Young (4-month-old) and old (20-month-old) rats, maintained under water restriction, were trained to discriminate to obtain a small amount of drinking water as a reward. Each animal had to learn to press a lever corresponding to a light that was randomly distributed on the left or right. Introduction of an auditory perturbation ("stress") during the discriminative phase of learning modified the capacity and rate of acquisition in both young and old animals, changes that were correlated with increases in plasma concentrations of epinephrine, norepinephrine and corticosterone. Stress-induced detrimental changes in both discrimination learning and plasma hormones were suppressed by 20 days of oral treatment with an extract of Ginkgo biloba leaves (EGb 761; 50 or 100 mg/kg/day) in both young and old rats, effects that became statistically significant by the third day of learning (time of maximal acquisition rate). EGb 761 treatment was less effective in increasing the percentage of efficient lever presses in old than in young rats, but more effective in decreasing the number of inefficient lever presses and reaction time in the older animals. These results indicate that EGb 761 can facilitate behavioral adaptation despite adverse environmental influences, a property that supports its clinical use in treating cognitive impairment, especially in elderly patients.
(REFERENCE 2 OF 24)
Tan MS, Yu JT, Tan CC, Wang HF, Meng XF, Wang C, Jiang T, Zhu XC, Tan L
Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis.
In: J Alzheimers Dis. 2015;43(2):589-603. doi: 10.3233/JAD-14083
Research into Ginkgo biloba has been ongoing for many years, while the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive impairment and dementia has been discussed controversially.
OBJECTIVE: To discuss new evidence on the clinical and adverse effects of standardized Ginkgo biloba extract EGb761 for cognitive impairment and dementia.
METHODS: MEDLINE, EMBASE, Cochrane, and other relevant databases were searched in March 2014 for eligible randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with cognitive impairment and dementia.
RESULTS: Nine trials met our inclusion criteria. Trials were of 22-26 weeks duration and included 2,561 patients in total. In the meta-analysis, the weighted mean differences in change scores for cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18; -2.54); the standardized mean differences in change scores for activities in daily living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI -0.44; -0.28); Peto OR showed a statistically significant difference from placebo for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54; 2.29). All these benefits are mainly associated with EGb761 at a dose of 240 mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240 mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric symptoms with statistical superiority than for the whole group. For the Alzheimer's disease subgroup, the main outcomes were almost the same as the whole group of patients with no statistical superiority. Finally, safety data revealed no important safety concerns with EGb761.
CONCLUSIONS: EGb761 at 240 mg/day is able to stabilize or slow decline in cognition, function, behavior, and global change at 22-26 weeks in cognitive impairment and dementia, especially for patients with neuropsychiatric symptoms.
(REFERENCE 3 OF 24)
Allain H Raoul P Lieury A LeCoz F Gandon JM d'Arbigny P
Effect of two doses of Ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects.
In: Clin Ther (1993 May-Jun) 15(3):549-58
The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms. The dual-coding phenomenon (a break point between coding verbal material and images) was demonstrated in all the tests. After placebo, the break point was observed at 960 ms and dual coding beginning at 1920 ms. After each dose of the ginkgo extract, the break point (at 480 ms) and dual coding (at 960 ms) were significantly shifted toward a shorter presentation time, indicating an improvement in the speed of information processing.
(REFERENCE 4 OF 24)
Amieva H1, Meillon C, Helmer C, Barberger-Gateau P, Dartigues JF.
Ginkgo biloba extract and long-term cognitive decline: a 20-year follow-up population-based study.
In: PLoS One. 2013;8(1):e52755. doi: 10.1371/journal.pone.0052755. Epub 2013 Jan 11
BACKGROUND: Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period.
METHODS AND FINDINGS: The data were gathered from the prospective community-based cohort study 'Paquid'. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the 'neither treatment' group. These effects were in opposite directions: the EGb761® group declined less rapidly than the 'neither treatment' group, whereas the piracetam group declined more rapidly (β = -0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the 'neither treatment' group (respectively, β = 0.21 and β = -0.03), whereas the piracetam group declined more rapidly (respectively, β = -1.40 and β = -0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively β = -1.07, β = -1.61 and β = -0.41).
CONCLUSION: Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam.
(REFERENCE 5 OF 24)
Rai GS Shovlin C Wesnes KA
A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment.
In: Curr Med Res Opin (1991) 12(6):350-5
Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks.
(REFERENCE 6 OF 24)
[Effect of Ginkgo-biloba extract on mental performance. Double-blind study using computerized measurement conditions in patients with cerebral insufficiency]
In: Fortschr Med (1992 Feb 20) 110(5):73-6 (Published in German)
Problem: The effect of ginkgo biloba extract EGb 761 on basic parameters of mental performance. Patients: Seventy-two outpatients with cerebral insufficiency at three test centers. Study design: Double-blind, randomized placebo-controlled study of 24 weeks duration. Test parameters: Psychometric computer-aided examination of the short-term memory and basic learning rate. Results: Statistically significant improvement in the short term memory after 6 weeks and of the learning rate after 24 weeks in the test substance group, but not in the placebo group (longitudinal analysis). The difference between the test substance and placebo groups (horizontal analysis) reached statistical significance in the 24th week. Conclusions: Treatment with ginkgo biloba extract EGb 761 improves mental/mnestic performance.
(REFERENCE 7 OF 24)
Zhang HF, Huang LB, Zhong YB, Zhou QH, Wang HL, Zheng GQ, Lin Y
[An Overview of Systematic Reviews of Ginkgo biloba Extracts for Mild Cognitive Impairment and Dementia.In: Fortschr Med (1990 Oct 10) 108(29):557-60 (Published in German)]
In: Front Aging Neurosci. 2016 Dec 6;8:276. doi: 10.3389/fnagi.2016.00276. eCollection 2016
Ginkgo biloba extracts (GBEs) have been recommended to improve cognitive function and to prevent cognitive decline, but earlier evidence was inconclusive. Here, we evaluated all systematic reviews of GBEs for prevention of cognitive decline, and intervention of mild cognitive impairment (MCI) and dementia. Six databases from their inception to September 2015 were searched. Ten systematic reviews were identified, including reviews about Alzheimer's disease (n = 3), about vascular dementia (n = 1), about both Alzheimer's disease and vascular dementia (n = 2), about Alzheimer's disease, vascular dementia and mixed dementia (n = 3), and a review about MCI (n = 1). Based on the overview quality assessment questionnaire, eight studies were scored with at least 5 points, while the other two scored 4 points and 3 points, respectively. Medication with GBEs showed improvement in cognition, neuropsychiatric symptoms, and daily activities, and the effect was dose-dependent. Efficacy was convincingly demonstrated only when high daily dose (240 mg) was applied. Compared with placebo, overall adverse events and serious adverse events were at the same level as placebo, with less adverse events in favor of GBE in the subgroup of Alzheimer's disease patients, and fewer incidences in vertigo, tinnitus, angina pectoris, and headache. In conclusion, there is clear evidence to support the efficacy of GBEs for MCI and dementia, whereas the question on efficacy to prevent cognitive decline is still open. In addition, GBEs seem to be generally safe.
(REFERENCE 8 OF 24)
Hashiguchi M, Ohta Y, Shimizu M, Maruyama J, Mochizuki M.
[Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia.In: J Fr Ophtalmol (1988) 11(10):671-4 (Published in French)]
In: J Pharm Health Care Sci. 2015 Apr 10;1:14. doi: 10.1186/s40780-015-0014-7. eCollection 2015.
The benefit of Ginkgo biloba for the treatment of dementia remains controversial. The aim of this study was to evaluate the efficacy and safety of Ginkgo biloba in patients with dementia in whom administration effects were reported using meta-analysis.
METHODS: We searched MEDLINE, Embase, the Cochrane databases, and Ichushi for controlled trials of Ginkgo biloba for the treatment dementia. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as standard mean differences (SMDs) in scores of the Syndrome Kurztest (SKT), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) for cognition efficacy, or odds ratios (ORs) for dropouts and adverse drug reactions.
RESULTS: Thirteen studies using the extract EGb761 met our inclusion criteria, which were duration of 12 to 52 weeks and daily dose of more than 120 mg, and included a total of 2381 patients. Meta-analysis was performed by using 9 of 13 studies, 7 of which used the SKT and 2 ADAS-Cog (dose 120 mg, 26 weeks) scores as efficacy parameters. In meta-analysis of all patients, SMDs (95% confidence interval [CI]) in the change in SKT scores (7 studies) were in favor of Ginkgo biloba over placebo (SMD = -0.90 [-1.46, -0.34]), but 2 studies that used ADAS-Cog did not show a statistically significant difference from placebo for ADAS-Cog (-0.06 [-0.41, 0.30]). For Alzheimer's disease (AD) and vascular dementia (VaD) subgroups, SMDs [95% CI] in SKT in the combined AD and VaD subgroup (-1.07 [-1.66, -0.47]) and AD subgroup (-1.36 [-2.27, -0.46]) were in favor of Ginkgo biloba over placebo. In terms of daily dose of Ginkgo biloba in the combined AD and VaD subgroup, SMD in SKT score in 240-mg daily dose groups was significantly greater than with placebo (-0.71 [-1.28, -0.14]). Dropout rates for any reason did not differ between two groups, but dropout rates due to side effects were significantly lower in Ginkgo biloba groups compared with placebo groups (OR = 1.72 [1.06, 2.80]).
CONCLUSIONS: Taking a 240-mg daily dose of Ginkgo biloba extract is effective and safe in the treatment of dementia.
(REFERENCE 9 OF 24)
Bruel A Gardette J Berrou E Droy-Lefaix MT Picard J
Effects of Ginkgo biloba extract on glucose transport and glycogen synthesis of cultured smooth muscle cells from pig aorta.
In: Pharmacol Res (1989 Jul-Aug) 21(4):421-9
We have examined the effect of an extract of Ginkgo biloba (Gbe) on glucose uptake and on glycogen synthesis in cultured smooth muscle cells (SMC) from pig aorta. Initial rates of glucose transport were determined by measurements of 2-deoxy-D-glucose (2-DG) uptake. From kinetic analyses apparent KM and Vmax values of facilitated glucose transport in cultured SMC were evaluated at 2.2 mM and 9.1 nmol/min/10(6) cells respectively. Gbe stimulated glucose transport in a dose-dependent manner; the maximum effect was reached at a Gbe concentration of 0.25 micrograms/ml and represented an increase of 35 +/- 4% above basal activity. This stimulation mainly occurred on facilitated glucose transport. The passive diffusion measured when cells were treated with cytochalasin B represented 15 +/- 3% of glucose total transport activity either in the absence or the presence of Gbe. The effect of Gbe on glycogen synthesis in cultured SMC was then tested by the incorporation of U14C-glucose into cellular glycogen. This process was enhanced by Gbe, the maximal effect was observed at a Gbe concentration of 0.25 micrograms/ml, and represented a 41 +r4% increase above basal activity. These data argue for a direct effect of Gbe upon glucose transport and glucose utilization in cultured SMC thus allowing a better nutriment disposal in the vascular wall.
(REFERENCE 10 OF 24)
Otamiri T Tagesson C
Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia.
In: Scand J Gastroenterol (1989 Aug) 24(6):666-70
We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.
(REFERENCE 11 OF 24)
Koltringer P Eber O Klima G Rothlauer W Wakonig P Langsteger W Lind P
[Microcirculation in parenteral Ginkgo biloba extract therapy]
In: Wien Klin Wochenschr (1989 Mar 17) 101(6):198-200 (Published in German)
15 patients with arteriosclerotic lesions in the extracranial brain arteries, randomly selected, were treated with an infusion of 250 ml physiological NaCl and 25 ml Ginkgo biloba extract (Tebonin). A second group (n = 15) received 250 ml NaCl without drugs stimulating blood flow. The skin microcirculation was measured in vivo by means of a helium-neon laser at one of the 4 extremities. Perfusion increased significantly (p less than or equal to 0.01) in response to Ginkgo biloba extract as compared with the response in the control group. The results justify the administration of Ginkgo biloba extract in vascular diseases.
(REFERENCE 12 OF 24)
Schaffler K Reeh PW
[Double blind study of the hypoxia protective effect of a standardized Ginkgo biloba preparation after repeated administration]
In: Arzneimittelforschung (1985) 35(8):1283-6 (Published in German)
A randomised, placebo-controlled, double-blind, crossover study was run in 8 healthy, male subjects (mean age 27.3 +/- 2.6 years, mean BW 75.3 +/- 9.7 kg) to demonstrate a possible hypoxia-protective effect of standardised Ginkgo flavone glycosides after subchronical administration. After a 14-days' treatment with Ginkgo biloba extract (Tebonin) performance of subjects was studied--concerning assessments of oculomotor and complex choice reaction system as well as simple cardiorespiratory parameters under multiple exposure to hypoxic hypoxia (10.5% oxygen, 89.5% nitrogen)--using oculodynamic methodology (ODT). Hypoxia increased the corneoretinal resting-potential of the eye and stimulated respiration. Both parameters were significantly reduced by verum administration. Under cumulative exposure to hypoxic hypoxia fixation time of saccadic eye movements and complex choice reaction time were significantly improved by Ginkgo flavone glycosides vs placebo. These results could be explained as a hypoxia-protective phenomenon--supporting the therapy of cerebral insufficiency.
(REFERENCE 13 OF 24)
[Clinical psychopharmacology of Ginkgo biloba extract]
In: Presse Med (1986 Sep 25) 15(31):1595-604 (Published in French)
From this general review of the pharmacological, psychopharmacological and clinical studies performed with Ginkgo biloba extract, the following conclusions can be drawn: the drug seems to be effective in patients with vascular disorders, in all types of dementia and even in patients suffering from cognitive disorders secondary to depression, because of its beneficial effects on mood. Of special concern are people who are just beginning to experience deterioration in their cognitive function. Ginkgo biloba extract might delay deterioration and enable these subject to maintain a normal life and escape institutionalization. In addition, Ginkgo biloba extract appears to be a safe drug, being well tolerated, even in doses many times higher than those usually recommended.
(REFERENCE 14 OF 24)
[Activity of Ginkgo biloba extract on short-term memory]
In: Presse Med (1986 Sep 25) 15(31):1592-4 (Published in French)
Eight healthy female volunteers were included in a double-blind, cross-over trial comparing Ginkgo biloba extract in acute and ascending doses (120, 240, 600 mg) with a placebo. One hour after treatment they were subjected to a battery of tests, including: critical flicker fusion, choice reaction time, subjective rating scale and Sternberg memory scanning test. No statistically significant differences with the placebo were observed in the first three tests. In contrast, short term memory, as assessed by the Sternberg technique, was very significantly improved following 600 mg of Ginkgo biloba extract, as compared with the placebo. These results differentiate Ginkgo biloba extract from sedative and stimulant drugs and suggest a specific effect on memory processes.
(REFERENCE 15 OF 24)
Taillandier J Ammar A Rabourdin JP Ribeyre JP Pichon J Niddam S Pierart H
[Treatment of cerebral aging disorders with Ginkgo biloba extract. A longitudinal multicenter double-blind drug vs. placebo study]
In: Presse Med (1986 Sep 25) 15(31):1583-7 (Published in French)
The effectiveness of Ginkgo biloba extract in the treatment of cerebral disorders due to ageing was evaluated in a multicentric, double-blind, drug versus placebo trial involving 166 patients. In this study carried out under strict methodological conditions a specially devised geriatric clinical evaluation scale was used. The results confirmed that Ginkgo biloba extract is effective against cerebral disorders due to ageing. The difference between control and treatment groups became significant at 3 months and increased during the following months. These results were concordant with the overall clinical assessment made by the specialist in charge.
(REFERENCE 16 OF 24)
Haguenauer JP Cantenot F Koskas H Pierart H
[Treatment of equilibrium disorders with Ginkgo biloba extract. A multicenter double-blind drug vs. placebo study]
In: Presse Med (1986 Sep 25) 15(31):1569-72 (Published in French)
This study, conducted in 3 centres, included 70 patients with vertiginous syndrome of recent onset and undetermined origin. In a double-blind trial extending over a 3-month period they were given either Ginkgo biloba extract or a placebo. The effectiveness of Ginkgo biloba extract on the intensity, frequency and duration of the disorder was statistically significant. At the end of the trial, 47% of the patients treated were rid of their symptoms as against 18% of those who received the placebo.
(REFERENCE 17 OF 24)
[Ginkgo biloba extract in the treatment of arteriopathy of the lower extremities. A 65-week trial]
In: Presse Med (1986 Sep 25) 15(31):1546-9 (Published in French)
Thirty-six patients with arteritis were treated with Ginkgo biloba extract for sixty-five weeks. For the first six months of the treatment period, these patients participated in a double-blind randomised comparison with 35 well matched patients taking placebo. Subsequently, those patients taking Ginkgo biloba extract were given the option to continue treatment on an open basis with follow-up at regular three-monthly intervals. Ginkgo biloba extract therapy gave significantly greater pain relief and walking tolerance than the placebo after 6 months of treatment, and this improvement continued throughout the whole duration of the study. This symptomatic and measurable improvement was combined with excellent tolerance of the drug.
(REFERENCE 18 OF 24)
Tamborini A Taurelle R
[Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome]
In: Rev Fr Gynecol Obstet (1993 Jul-Sep) 88(7-9):447-57 (Published in French)
The efficacy of standardized Ginkgo biloba extract (EGb 761) in treating congestive symptoms of premenstrual syndrome (PMS) was evaluated in a controlled multicentric double blind study versus placebo. The population studied was a group of 165 women aged between 18 to 45, in genital activity period, suffering since 3 cycles from congestive premenstrual troubles during at least 7 days per cycle. The characteristics of patients and PMS were the same in both groups (EGb 761 and placebo). The observation of one menstrual cycle confirmed the diagnosis of PMS. Then, during the 2 following cycles, each patient received either EGb 761 or placebo from the 16th day of the first cycle till the 5th day of the next cycle. A double evaluation of the symptoms was realized by the patient using a daily rating scale (auto-evaluation), by the practitioner during visits at the premenstrual phase before and after the two cycles treatment. From 165 patients included, 143 observations were available. With a good acceptability, EGb 761 was effective against the congestive symptoms of PMS, particularly breast symptoms with a statistical significance between EGb 761 and placebo. Neuropsychological symptoms were also improved. EGb 761 is an alternative of interest to therapeutics already used in treating PMS or can be associated without any inconvenience.
(REFERENCE 19 OF 24)
[Treatment of the disorders of aging with Ginkgo biloba extract. From pharmacology to clinical medicine]
In: Presse Med (1986 Sep 25) 15(31):1540-5 (Published in French)
Ginkgo biloba extract is prescribed in psychic and behavioural disorders of the elderly, in peripheral vascular deficiency and in functional disorders of ischaemic origin in the E.N.T. and eye areas. Numerous controlled clinical trials justify these prescriptions and are in agreement with the pharmacological data currently available. Experimentally, Ginkgo biloba extract has proved active on the circulatory and rheological functions, on neuronal metabolism threatened by ischaemia or hypoxia, on neurotransmission and on membrane lesions caused by free oxygenated radicals. Concerning Alzheimer's disease and dementia, no firm conclusion can be drawn for the time being due to the lack of animal model. However, experimental data suggest that the product may act on a number of major elements of these diseases. From what is already known about Ginkgo biloba extract, it appears that it fulfills the conditions laid down by the W.H.O. concerning the development of drugs effective against cerebral ageing.
(REFERENCE 20 OF 24)
[From the body to the cell membrane: the different levels of pharmacological action of Ginkgo biloba extract]
In: Presse Med (1986 Sep 25) 15(31):1529-38 (Published in French)
The pharmacological study of Ginkgo biloba extract has required numerous experiments over several years: different pathological models of cerebral ischaemia to evaluate its effects, and experiments at both cellular and molecular levels to determine its mechanisms of action. In experimental models of ischaemia, oedema and hypoxia, Ginkgo biloba extract reduced vascular, tissular and metabolic disturbances as well as their neurological and behavioural concern vascular, rheological and metabolic processes. Several membrane mechanisms seem to be involved: protection of the membrane ultrastructure against free radicals, modulation of some enzymatic systems and ionic pumps. The originality of the pharmacological properties of Ginkgo biloba extract lies in preferential focusing of its effects on ischaemic areas.
(REFERENCE 21 OF 24)
Auguet M Delaflotte S Hellegouarch A Clostre F
[Pharmacological bases of the vascular impact of Ginkgo biloba extract]
In: Presse Med (1986 Sep 25) 15(31):1524-8 (Published in French)
The preferential tissue irrigatory effect of Ginkgo biloba extract in ischaemic areas is largely explained by the direct impact of this product on both arteries and veins. The adrenergic vasoregulatory system and the vascular endothelium are the preferential targets for arterial impact. Ginkgo biloba extract reinforces the physiological vasoregulation of the sympathetic nervous system directly, by acting on neuromediator release, and indirectly, by inhibiting their extraneuronal degradation by catechol-orthomethyltransferase (C.O.M.T.). In the arterial endothelium Ginkgo biloba extract stimulates the release of endogenous relaxing factors, such as endothelium-derived relaxing factor, (EDRF) and prostacyclin. The action of Ginkgo biloba extract on the venous system has been shown to have a venoconstrictor component that maintains the degree of parietal tonus essential to the dynamic clearing of toxic metabolites accumulated during tissue ischaemia. The originality of the vascular impact mechanisms of Ginkgo biloba extract is due to the fact that the product can at the same time combat the phenomena resulting from vascular spasm and with the same efficiency restore circulation in areas subject to vasomotor paralysis.
(REFERENCE 22 OF 24)
Etienne A Hecquet F Clostre F
[Mechanism of action of Ginkgo biloba extract in experimental cerebral edema]
In: Presse Med (1986 Sep 25) 15(31):1506-10 (Published in French)
Oedema is one of the major complication of cerebral ischaemia being at the same time a consequence and an aggravating factor. Its first phase is intracellular and cytotoxic, with breakdown of ionic pumps through loss of energy, resulting in a whole sequence of ionic perturbations characterized by loss of intracellular K+ and accumulation of water and Na+, Cl-, and Ca2+ ions in the cells of the ischaemic zone. The second phase, termed vasogenic, applies to the accumulation of lactates, inorganic phosphates and free polyunsaturated fatty acids and in particular, arachidonic acid. This last compound is responsible for the production of membrane "aggressors", amongst which free radicals play an important role. Ginkgo biloba extract limits the formation of cerebral oedema and suppresses its neurological consequences, whether the oedema is of cytotoxic (triethyltin) or vasogenic (unilateral traumatic oedema) origin. Several membrane mechanisms could be implicated in the protective action manifested by Ginkgo biloba extract against cerebral oedema.
(REFERENCE 23 OF 24)
Racagni G Brunello N Paoletti R
[Neuromediator changes during cerebral aging. The effect of Ginkgo biloba extract]
In: Presse Med (1986 Sep 25) 15(31):1488-90 (Published in French)
Ginkgo biloba extract exerts a specific effect on the noradrenergic system and on beta-receptors. No variation was found in alpha 2-receptors and serotonin uptake. These findings provide the first evidence of central effects of a drug acting on cerebral ageing, connected specifically to reactivation of the noradrenergic system in the cerebral cortex.
(REFERENCE 24 OF 24)
6-Month double-blind randomised clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency.
In: Arzneimittelforschung (1984) 34(6):716-20
79 patients suffering from peripheral arteriopathy (Fontaine's stage IIb) completed a 6-month double-blind randomised clinical trial of Ginkgo biloba extract (GBE) (as coated tablets containing 40 mg GBE; rokan) versus placebo in two parallel groups. From the results of measurements of pain-free walking distance, maximum walking distance and plethysmography recordings, GBE was shown to be active and significantly superior to placebo. These results correlated with the physician's and patients' overall assessment of response to treatment.
Droy-Lefaix MT Bonhomme B Doly M
Protective effect of Ginkgo biloba extract (EGB 761) on free radical-induced changes in the electroretinogram of isolated rat retina.
In: Drugs Exp Clin Res (1991) 17(12):571-4
The retina is a tissue particularly rich in polyunsaturated fatty acids and thus highly sensitive to lipid peroxidation initiated by oxygenated free radicals. By recording the electroretinogram (ERG) b wave amplitude on isolated rat retina, the authors have investigated the anti-oxidant properties of Ginkgo biloba extract (EGB 761). Two groups of rats were used: one group was treated with EGB 761 at a dose of 100 mg/kg/day per os for 10 days; the other one of untreated animals served as a control. At the end of the treatment (10 days), rats were sacrificed, one retina isolated and perfused in order to record ERG. Lipid peroxidation was induced by adding a mixture of (FeSO4 + Na ascorbate) to the perfusion solution. In the untreated rats a 50% decrease in ERG was observed after only 55 min. Such a delay in the decrease and subsequent maintenance of ERG b wave amplitude confirm that the anti-oxidant properties of EGB 761 can protect the retina against lipoperoxidation.
Huguet F Drieu K Piriou A
Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761).
In: J Pharm Pharmacol (1994 Apr) 46(4):316-8
Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.
[Cerebral insufficiency--treatment with Ginkgo-biloba extract. Time of onset of effect in a double-blind study with 60 inpatients]
In: Fortschr Med (1990 Oct 10) 108(29):557-60 (Published in German)
Sixty inpatients with cerebral insufficiency and the leading symptom depressive mood, were treated in a double-blind study for 6 weeks with a daily dose of 160 mg Ginkgo biloba extract or placebo. After 2, 4 and 6 weeks, changes in 12 typical symptoms in comparison with the last examination, were evaluated. In the group receiving placebo, small, but progressive improvements were observed. In the Ginkgo biloba group, the overall number of improvements was significantly larger. After 2 weeks the differences were marked for only a few of the symptoms; after 4 and 6 weeks in contrast, in 11 of the 12 symptoms. The largest number of improvements in the Ginkgo-bilobagroup was observed between the 2nd and 4th weeks of treatment. In this period, about two-thirds of the patients on Ginkgo-biloba, and about one-fifth of the patients on placebo showed improvements.
Lanthony P Cosson JP
[The course of color vision in early diabetic retinopathy treated with Ginkgo biloba extract. A preliminary double-blind versus placebo study]
In: J Fr Ophtalmol (1988) 11(10):671-4 (Published in French)
The therapeutic efficiency of the Ginkgo biloba extract was estimated in a double-blind trial, during a 6 months period, in 29 diabetic subjects with an early diabetic retinopathy evidenced by angiography, and associated with a blue-yellow dyschromatopsia. The functional criterion was the color vision evolution, studied by the Desaturated Panel D-15 and the 100-Hue Farnsworth test at the beginning of the trial and 6 months later. An improvement tendency was evidenced in subjects treated by Ginkgo biloba extract, and an aggravation in subjects with placebo, this improvement being statistically significative with the Desaturated Panel D-15 among subjects without retinal ischemia. These clinical results on visual function corroborate the pharmacological actions of Ginkgo biloba extract on diabetic retina.