Ginkgo Biloba

An abundance of research has been undertaken on this ancient
plant, revealing a wide range of profound and important therapeutic effects.
They can be grouped into cardiovascular, neurological and metabolic effects.
Here we shall focus on the cardiovascular indications. Please refer to the
sections on the nervous system and immune support for a review of the rest of Ginkgo’s uses.

Laboratory research on Ginkgo’s cardiovascular effects

In one test, microscopic particles were injected into the carotid
artery of rats, mimicking arterial blockage. Ginkgo protected the unfortunate animals from the destructive effects. increased levels of glucose and ATP were found, thus helping to maintain energy levels within individual cells.

It reduced the tendency for thrombus formation in veins and arteries,
suggesting a use in the prevention of coronary thrombosis and in recovery from strokes and heart attacks.

Following injections there may be a hypertensive response, damaging the blood-brain barrier. Initially only small molecules pass the barrier, but eventually larger substances cross over causing cerebral edema. Ginkgo used in the initial stages prevents the later stages developing. Stabilizing the membranes of the blood-brain barrier which are thought to involve a direct impact on ionic balance across the membranes and an indirect effect on intracellular respiration, lessening cerebral edema and restoring function.

Clinical research

    • it lowered blood pressure and dilated peripheral blood vessels, in patients
      recovering from thrombosis.
    • microcirculation in the conjunctiva of patients with disturbances in cerebral
      blood supply consistently increased. Capillary and venous blood flow to the
      head increased because of decreased resistance to flow occurred. A toning
      action occurs as it eases venular spasms that often occur in elderly and
      arteriosclerotic patients. The herb can combat both vascular spasm and restore
      tone and circulation in areas subject to vasomotor paralysis.
    • it increases peripheral blood flow with no lessening of cerebral circulation.
      Chemical vaso-dilators accumulate in the expanded vessels rather than circulate
      to the veins that feed the central nervous system. Ginkgo, however, increasing
      blood flow to both the periphery and the brain.
    • in patients with peripheral arterial insufficiency improvement in all
      experimental measures, including the ability to walk without pain and blood
      flow to the legs.
    • in Parkinson’s disease secondary to cerebral arteriosclerosis, the herb
      increased blood supply to the brain.
    • 65% successful treatment of focal or diffuse cerebral vascular disease.
    • 80% successful treatment of cerebral circulatory insufficiency, measured as
      improvement in mental functioning, EEG parameters, and cerebral angiogram.
    • 80% success rate in patients with chronic cerebral insufficiency measured by
      symptoms such as vertigo, headache.
    • 92% success rate in patients with cerebrovascular insufficiency and all
      pathological findings disappeared after 18 days of treatment.
    • 80% success in treating headache and lesser per cent success in case of
      migraine.
    • 40% success in elderly patients with arterial insufficiency of lower limbs.
    • 72% success in the treatment of chronic vasculopathies.
    • successful treatment of chronic arterial obliteration.Patients with organic and neurological angiopathy were observed for
      physiological changes resulting from exercise, after using Ginkgo. Results indicate it would be useful in central and peripheral vascular disease, including diabetic angiopathy.

Therapeutic Uses

Ginkgo has wide application for treating various forms of vascular and
neurological disease. It has been recommended for:

  • vertigo, headache, tinnitus, inner ear disturbances including partial deafness
  • impairment of memory and ability to concentrate
  • diminished intellectual capacity and alertness as a result of insufficient
    circulation
  • anxiety, depression, neurological disorders : complications of stroke and skull injuries
  • diminished sight and hearing ability due to vascular insufficiency
  • intermittent claudication as a result of arterial obstruction
  • a sensitivity to cold and pallor in the toes due to peripheral circulatory insufficiency
  • Raynaud’s disease: cerebral vascular and nutritional insufficiency
  • hormonal and neural based disorders as well as angiopathic trophic
    disorders
  • arterial circulatory disturbances due to aging, diabetes and nicotine abuse
  • sclerosis of cerebral arteries with and without mental manifestations
  • arteriosclerotic angiopathy of lower limbs
  • diabetic tissue damage with danger of gangrene : chronic arterial obliteration
  • circulatory disorders of the skin, as well as ulcerations caused by
    ischaemia.

Constituents


acacetin

acenapthene

acetic-acid

afzelin

alanine

amentoflavone

g-aminobutyric-acid

anacardic-acid

apigenin

arabinose

arginine

ascorbic-acid

ash

asparagine

aspartic-acid

betulaprenols

bilobalide

bilobanone

bilobetin

bilobol

butyric-acid

calcium

calcium-oxalate

caproic-acid

caprylic-acid

carbohydrates

cardanol

cardol

beta-carotene

d-catechin

ceryl-alcohol tw

citric-acid

copper

p-coumaric-acid

p-cymene

cysteine

cystine

-(e)-dihydroatlantone jsg

-(z)-dihydroatlantone jsg

-dimethyl–diiso-propylbenzene

dna – fl(male)

docosanol

elemol

l-epicatechin

l-epigallocatechin

alpha-ethyllathosterol

beta-eudesmol

gamma-eudesmol

fat

fiber

formic-acid

uctose

gadoleic-acid

galactose

d-gallocatechin

ginkgetin

ginkgol

ginkgolic-acid

ginkgolide-a

ginkgolide-acid

ginkgolide-b

ginkgolide-c

ginkgolide-m

ginnol

ginnon

d-glucaric-acid

glucomannan

glucose

glutamic-acid

glycine

-heptacosanol

hexacosanol

alpha-hexenal

histidine

homoserine

hydroginkgolic-acid

-hydroxyanacardic-acid

-hydroxyginkgolic-acid

-hydroxykynurenic-acid

alpha-ionone

beta-ionone

ipuranol

iron

isoginkgetin

isoleucine

-isopropylphenol

isorhamnetin

kaempferol

kaempferol–o-alpha(”’-p-coumaroyl-glucosyl-beta–rhamnoside)

kaempferol–rhamno-glucoside

kaempferol–rutinoside

leucine

trans-linalool-oxide

linoleic-acid

alpha-linolenic-acid

luteolin

lysine

magnesium

manganese

mannan

mannose

methionine

‘-methoxybilobetin

‘-methoxypyridoxine

‘-o-methylmyricetin–rutinoside

myristic-acid

niacin

nonacosane

-nonacosanol

-nonacosanol

octacosanol

oleic-acid

-(e)–oxo-dihydroatlantone

palmitic-acid

palmitoleic-acid

pantothenic-acid

-(pentadec–enyl)–di-hydroxybenzoic-acid

zz’-(-pentadien–diyl)diphenol

pentosans

pentosans

phenylalanine

phosphorus

pinitol

pulnin

tassium

procyanidin

prodelphinidin

proline

propionic-acid

protein

quercetin

quercetin–o-alpha(”’-p-coumaroyl-glucosyl-beta–rhamnoside)

quercetin–rhamnoglucoside

quercetin–rutinoside

quinic-acid

raffinose

raffinose

riboflavin

sciadopitysin

sequoyitol

serine

alpha-sesamin

shikimic-acid

sitosterol

sodium

spinasterol

starch

stearic-acid

stigmasterol

succinic-acid

sucrose

sucrose

tannin

thiamin

threonine

thymol

p-tolyl-propylene

tricetin

-trimethyl-dihydronaphthalene

tryptophan

tyrosine

uroshiols

valerianic-acid

valine

wax

xylose

zinc


Citations from the Medline database for the genus Ginkgo


Agnoli A.

Clinical and psychometric aspects of the therapeutic effects of GBE.

In: Effects of GBE and Organic Cerebral Impairment, Paris, London, John
Lilley, 1985.

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.

Allard M

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.

Apaydin C Oguz Y Agar A Yargicoglu P Demir N Aksu G

Visual evoked potentials and optic nerve histopathology in normal and
diabetic rats and effect of ginkgo biloba extract.

In: Acta Ophthalmol (Copenh) (1993 Oct) 71(5):623-8

The purpose of this study was to test the possible therapeutic role of ginkgo
biloba extract on the impairment of visual function and pathological histology
of the optic nerve caused by early diabetes. Ginkgo biloba extract entraps
oxygenated free radicals and is also a strong inhibitor of the platelet
activation factor (PAF). For this purpose, VEP recordings and optic nerve
histopathology were studied on alloxan diabetic and normal Swiss albino rats
in four experimental groups. The VEP recordings showed no statistical
significance between diabetic and normal rats. However, the amplitudes were
significantly increased in diabetic animals with ginkgo biloba extract
compared with the diabetics, supposing an impression of axonal protection. But
the amplitude values were decreased in normal rats treated with the same
extract compared with normal animals, assuming a toxic activity. Optic nerve
ultrastructural findings also confirmed these VEP changes. It was concluded
that this extract could be encouraging for human clinical trials of
diabetes.

Atzori C Bruno A Chichino G Bombardelli E Scaglia M Ghione M

Activity of bilobalide, a sesquiterpene from Ginkgo biloba, on Pneumocystis
carinii.

In: Antimicrob Agents Chemother (1993 Jul) 37(7):1492-6

The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested
in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth.
Bilobalide was inhibitory to trophozoites cultured on human embryonic lung
fibroblasts (HEL 299) at approximately the same concentration as trimethoprim
plus sulfamethoxazole (lowest effective concentration, 50 micrograms of
bilobalide per ml versus 9/45 microgram of trimethoprim- sulfamethoxazole per
ml), inducing microscopically detectable morphological changes in the
cytoplasm of the parasite. In pharmacologically immunosuppressed
Sprague-Dawley rats transtracheally infected with a suspension of about 5 x
10(6) P. carinii trophozoites per ml, the daily intraperitoneal administration
of bilobalide (10 mg/kg of body weight for 8 days) lowered the number of
organisms by approximately 2 logs (that is, about 99%). There was no apparent
toxicity either in uninfected HEL 299 feeder cells or in infected and
uninfected animals. These studies suggest that the sesquiterpene bilobalide
might be useful for therapy of and prophylaxis against P. carinii infections
in humans.

Bauer U.,

Six months double-blind randomised clinical trial of Ginkgo biloba extract
versus placebo in two parallel groups in patients suffering from peripheral
arterial insufficiency.

In: Arzneimittel – ForsehlDru: Res, 1984, 34, 716-720.

Boismare F.:

Etude de l’action hemodynamique de l’extrait concentre de Ginkgo biloba
comparee a celle du gaz carbonique chez le sujet jeune et chez le sujet senile.

In: Ouesl Medical, 1976, 29, 747-749.

Bono Y., Mouren P.:

L’insuffisance circulatoire cerebrale et son traitement par l’extrait de
Ginkgo biloba.

In: Med. Med., 1975, 3, 59-62.

Boudouresques G., Vigouroux R., Boudouresques J.:

Interet et place de l’extrait de Ginkgo biloba en pathologie vasculaire
cerebrale.

In: Medecine Pralicienne, 1975, 59:, 75-78.

Bourgain RH Maes L Andries R Braquet P

Thrombus induction by endogenic paf-acether and its inhibition by Ginkgo
Biloba extracts in the guinea pig.

In: PROSTAGLANDINS (1986 Jul) 32(1):142-4

The anti-thrombotic effects of specific paf-acether antagonist BN 52021 were
compared to the effects of Ginkgo Biloba extracts A, B, (A+ B), and C. Local
superfusion of BN 52021 over an experimentally injured arterial segment
embolizes an existent paf-acether induced platelet thrombus. When applied
before paf-acether, BN 52021 prevents local thromboformation in this model.
Applied intravenously, BN 52021 reduces local thromboformation in a significant
way. As compared to this BN 52021 standard, only Ginkgo Biloba B and the (A +
B)-mixture present major thromboreductive activity.

Braquet P

Cedemin, a Ginkgo biloba extract, should not be considered as a PAF
antagonist [letter; comment]

In: Am J Gastroenterol (1993 Dec) 88(12):2138

Chabrier PE Roubert P

[Effect of Ginkgo biloba extract on the hemato-encephalic barrier]

Effet de l’extrait de Ginkgo biloba sur la barriere hemo-encephalique.

In: Presse Med (1986 Sep 25) 15(31):1498-501

The different methods used to explore the blood-brain barrier (made up of
cerebral capillary vessels), and notably, at molecular level, isolated
microvessel preparations, have greatly improved our knowledge in this
particular field. Some of these methods could be used to evaluate the
protective effects of therapeutic substances, such as Ginkgo biloba extract, on
the blood-brain barrier.

Chaterjee G.:

Effects of Ginkgo biloba extract on cerebral metabolic processes.

In: Effects of GBE and Organic Cerebral Impairment, Paris, London, John
Lilley, 1985.

Clostre F

[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: diffe rent 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 consequences. The pharmacological effects of Ginkgo biloba extract
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.

Creutzig A

[Is Ginkgo biloba extract EGb 761 clinically effective in intermittent
claudication? (letter)]

In: Vasa (1993) 22(2):189-90 (Published in German)

Diwok M Kuklinski B Ernst B

[Superoxide dismutase activity of Ginkgo biloba extract]

In: Z Gesamte Inn Med (1992 Jul) 47(7):308-11 (Published in German)

The Ginkgo biloba extract is obtained from green leaves of the Ginkgo biloba
tree. Preparations with this active substance are among others used for the
treatment of disturbances of the cerebral function and arteriosclerotic
diseases. In in-vitro and in-vivo studies antagonistic effects of radical
scavenger and PAF (platelet activating factor) were described. In this study a
concentration- depending superoxide dismutase activity of the Ginkgo biloba
extract rokan liquid could be made evident.

Droy-Lefaix-M-T; Szabo-M-E; Doly-M

Ischaemia and reperfusion-induced injury in rat retina obtained from
normotensive and spontaneously hypertensive rats: Effects of free radical
scavengers.

In: International Journal of Tissue Reactions (1993)15(2): 85-91

The authors have studied the effects of free radical scavengers, superoxide
dismutase (SOD) and extract of Ginkgo biloba (EGb 761, flavone-rich extract) on
ion shifts (Na, K and Ca) induced by ischaemia and reperfusion in rat retina
obtained from normotensive and spontaneously hypertensive rats. Eyes were
subjected to 90 min of ischaemia by occlusion of the retinal artery, followed
by 4 and 24 hours of reperfusion. SOD (15, 000 U/kg, i.v.) or EGb 761 (50 mg/kg,
per os) was administered in a daily dose for 10 days. In the drug-free control
groups, 90 min of ischaemia significantly increased tissue Na gains from their
pre-ischaemic control values of 63 +- 7 mu-M/g dry weight (in retina obtained
from normotensive rats) and 76 mu-M/g dry weight (in retina obtained from
hypertensive rats) to 89 +- 9 mu-M/g dry weight and 101 +- 7 mu-M/g dry weight,
respectively. During reperfusion, a further elevation was found in retinal Na
in both the normotensive and hypertensive groups. Probably, because of the
ischaemia-induced inhibition of Na-K-ATPase, retinal K loss was detected after
ischaemia and reperfusion, respectively. An accumulation of retinal Ca was
measured after ischaemia and reperfusion in the normotensive and spontaneously
hypertensive groups. Both free radical scavengers significantly reduced the
maldistribution of ions induced by ischaemia and reperfusion, but the
effectiveness of drugs was more evident in normotensive than hypertensive
groups. The present results indicate that the elimination of free radicals by
free radical scavengers may reduce, probably via an indirect mode, the
reperfusion-induced ionic imbalance and improve the ionic homeostasis in
injured retinal cells obtained from normotensive and spontaneously hypertensive
rats.

Dumont E Petit E Tarrade T Nouvelot A

UV-C irradiation-induced peroxidative degradation of microsomal fatty acids
and proteins: protection by an extract of Ginkgo biloba (EGb761).

In: Free Radic Biol Med (1992 Sep) 13(3):197-203

After exposure of rat liver microsomes to UV-C irradiation, analysis of
membrane fatty acids by gas chromatography confirmed that EGb 761, a drug
containing a dosed and standardized extract of Ginkgo biloba, provides
effective protection against free radical attack in vitro. This analysis,
coupled with thiobarbituric acid (TBA) reaction, permitted qualitative and
overall quantitative evaluation of radical- induced damage to polyunsaturated
fatty acids (PUFA), as well as evidence of the antioxidant properties of the
Ginkgo biloba extract. Assay of thiobarbituric acid reactive substances
(TBARS) showed a correlation between TBARS concentration and the state of
degradation of the polyunsaturated fatty acids. Mannitol (5.5 mM) did not
prevent degradation of microsomal PUFA or malondialdehyde (MDA) production,
nor did it prevent polymerization of membrane proteins. Low doses of EGb 761
were found to provide efficient protection of membrane PUFA regardless of
individual susceptibility to peroxidation. This protection was accompanied by
a decrease in the production of TBARS. EGb 761 also protected membrane
proteins from the irreversible polymerization induced by these degradation
products, but did not appear to prevent thiols oxidation into disulfide
bonds.

Eckmann F., Schlag H.:

Etude controlee, a double insu, de l’activite de l’Extrait de Ginkgo biloba
chez des malades atteints d’insuffisance cerebrale chronique.

In: Fortschritte der Medizin, 1982, 31132, 1474-1478.

Etienne A Hecquet F Clostre F

[Mechanism of action of Ginkgo biloba extract in experimental cerebral
edema]

Mecanismes d’action de l’extrait de Ginkgo biloba sur l’oedeme cerebral
experimental.

In: Presse Med (1986 Sep 25) 15(31):1506-10

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.

Gautherie M Bourjat P Grosshans E Quenneville Y

[Vasodilator effect of Gingko biloba extract determined by skin thermometry
and thermography]

In: THERAPIE (Sep-Oct 72) 27(5):881-92

Gessner B Voelp A Klasser M

Study of the long-term action of a Ginkgo biloba extract on vigilance and
mental performance as determined by means of quantitative pharmaco-EEG and
psychometric measurements.

In: Arzneimittelforschung (1985) 35(9):1459-65

Gonda R Takeda K Shimizu N Tomoda M

Characterization of a neutral polysaccharide having activity on the
reticuloendothelial system from the rhizome of Curcuma longa.

In: Chem Pharm Bull (Tokyo) (1992 Jan) 40(1):185-8

A neutral polysaccharide, named ukonan D, was isolated from the rhizome of
Curcuma longa L. It produced a single band on electrophoresis and a single
peak on gel chromatography, and its molecular mass was estimated to be 28, 000.
It showed remarkable reticuloendothelial system-potentiating activity in a
carbon clearance test. Ukonan D is composed of L-arabinose: D-galactose: D-
glucose: D-mannose in the molar ratio of 1:1:12:0.2, in addition to small
amounts of peptide moiety. Methylation analysis, carbon-13 nuclear magnetic
resonance and enzymic degradation studies indicated that its structural
features include mainly both alpha-1, 5-linked L- arabino-beta-3, 6-branched
D-galactan type and alpha-4, 6-branched D- glucan type structural units. The
influence of degradation with alpha- amylase followed by the elimination of
glucan side chains on its immunological activity was discussed.

Gonda R Tomoda M Ohara N Takada K

Arabinogalactan core structure and immunological activities of ukonan C, an
acidic polysaccharide from the rhizome of Curcuma longa.

In: Biol Pharm Bull (1993 Mar) 16(3):235-8

Controlled Smith degradation of ukonan C, a phagocytosis-activating
polysaccharide isolated from the rhizome of Curcuma longa L., was performed.
The reticuloendothelial system-potentiating, anti- complementary and alkaline
phosphatase-inducing activities of ukonan C and its degradation products were
investigated. Methylation analyses of the primary and secondary Smith
degradation products and of a de-arabinosylated product indicated that
structural features of the arabinogalactan core of ukonan C include a backbone
chain composed of beta-1, 3-linked D-galactose and beta-1, 4-linked D-xylose.
All of the galactose units in the backbone carry side chains composed of
beta-1, 6-linked D-galactosyl residues with or without terminal
alpha-L-arabinose units at position 3. Ukonan C showed remarkable effects on
both reticuloendothelial system-potentiating and alkaline phosphatase-inducing
activities. Periodate oxidation caused a decrease in or disappearance of the
immunological activities, but the controlled Smith degradation product having
the arabinogalactan core structure of polysaccharide showed a pronounced
effect on anti- complementary activity.

Gonda R Tomoda M Takada K Ohara N Shimizu N

The core structure of ukonan A, a phagocytosis-activating polysaccharide
from the rhizome of Curcuma longa, and immunological activities of degradation
products.

In: Chem Pharm Bull (Tokyo) (1992 Apr) 40(4):990-3

The controlled Smith degradation of ukonan A, a phagocytosis- activating
polysaccharide isolated from the rhizome of Curcuma longa L., was performed.
The reticuloendothelial system-potentiating, anti- complementary and alkaline
phosphatase-inducing activities of ukonan A and its degradation products were
investigated. Methylation analyses of both the primary and the secondary Smith
degradation products indicated that the core structural features of ukonan A
include a backbone chain mainly composed of beta-1, 3-linked D- galactose,
beta-1, 4-linked D-xylose and alpha-1, 2-linked L-rhamnose residues. All of the
galactose units in the backbone carry side chains composed of
alpha-L-arabino-beta-D-galactosyl or beta-D- galactosyl residues at position
6. Ukonan A has a remarkable effect on each of the three kinds of
immunological activities. Periodate oxidation caused pronounced decrease or
disappearance of the activities, but the controlled Smith degradation product
having the core structure of polysaccharide showed considerable restoration of
these activities.

Grassel E

[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 shortterm 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.

Hitzenberger G

[The effect of ginkgo biloba special extract (EGb 761, Tebofortan)]

In: Wien Med Wochenschr (1992) 142(17):371-9 (Published in German)

Ginkgo biloba special extract exerts positive effects on hemorheology and
platelet aggregation, is a free radical scavenger and possesses PAD
antagonistic properties, protects against hypoxia and ischemia, hampers an
experimentally induced cerebral edema, has favourable properties on
neurotransmitters and enhances cerebral bloodflow. Clinically EGb has proven
favourable effects on intellectual deficiency, equilibrium disturbances and
peripheral artery occlusions thus being a drug with a clear cut indication for
these diseases.

Hofferberth, B.:

The influence of Ginkgo Biloba Extract (GBE) on the Neuro physiological and
Psychometrical Test results in patients suffering from organic cerebral
Psychosyndrome: A Double-Blind Study Versus Placebo.

In: Conference at The Third Congress of the International
Psychogeriatric Association, Chicago, August 1987

Hoffmann F Beck C Schutz A Offermann P

[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl

(Dusodril)/HAES. A randomized study of therapy of sudden deafness]

In: Laryngorhinootologie (1994 Mar) 73(3):149-52 (Published in German)

80 patients with idiopathic sudden hearing loss existing no longer than 10
days were included in a randomised reference-controlled study. The therapeutic
value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl
(Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating
activity (increased blood flow), the platelet activating factor antagonism and
a prevention of membrane damage caused by free radicals. Naftidrofuryl has
antiserotonergic and therefore vasodilatory properties. The statistical
analysis of the audiometric data was performed in measuring the relative
hearing gain as described by Eibach 1979. After one week of observation, 40%
of the patients in each group showed a complete remission of hearing loss.
This was also observed by other authors who had compared other drugs.
Therefore, in these cases, it is most likely that spontaneous recovery is the
most important factor. After two and three weeks of observation, measuring
the relative hearing gain, there was a significant borderline benefit of EGb
761 (p = 0.06) without any side effects. Some patients of the reference group
developed side effects such as orthostatic dysregulation or headache or sleep
disturbances. Minimising side effects should be one of the most important
goals in therapy of sudden hearing loss until the efficiency of infusion
therapy is proved.

Holgers KM Axelsson A Pringle I

Ginkgo biloba extract for the treatment of tinnitus.

In: Audiology (1994 Mar-Apr) 33(2):85-92

Previous studies have shown contradictory results of Ginkgo biloba extract
(GBE) treatment of tinnitus. The present study was divided into two parts:
first an open part, without placebo control (n = 80), followed by a
double-blind placebo-controlled study (n = 20). The patients included in the
open study were patients who had been referred to the Department of Audiology,
Sahlgren’s Hospital, Goteborg, Sweden, due to persistent severe tinnitus.
Patients reporting a positive effect on tinnitus in the open study were
included in the double-blind placebo-controlled study (20 out of 21 patients
participated). 7 patients preferred GBE to placebo, 7 placebo to GBE and 6
patients had no preference. Statistical group analysis gives no support to the
hypothesis that GBE has any effect on tinnitus, although it is possible that
GBE has an effect on some patients due to several reasons, e.g. the diverse
etiology of tinnitus. Since there is no objective method to measure the
symptom, the search for an effective drug can only be made on an individual
basis.

Huguet F Tarrade T

Alpha 2-adrenoceptor changes during cerebral ageing. The effect of Ginkgo
biloba extract.

In: J Pharm Pharmacol (1992 Jan) 44(1):24-7

[3H]Rauwolscine binding to alpha 2-adrenoceptors in cerebral cortex and
hippocampus membranes of young (4 months) and aged (24 months) Wistar rats has
been investigated. In aged rats, Bmax values of [3H]rauwolscine binding were
significantly reduced (25-32%) in the cerebral cortex and hippocampus, as
compared with the number of alpha 2-adrenoceptors found in young rats. Chronic
treatment with Ginkgo biloba extract did not alter [3H]rauwolscine binding in
the hippocampus of young rats, but significantly increased (28%) the
[3H]rauwolscine binding density in aged rats. These data confirm the
previously described age-related noradrenergic alteration and suggest that
noradrenergic activity in aged rats is more susceptible to Ginkgo biloba
extract treatment.

Kenzelmann R Kade F

Limitation of the deterioration of lipid parameters by a standardized
garlic-ginkgo combination product. A multicenter placebo-controlled
double-blind study.

In: Arzneimittelforschung (1993 Sep) 43(9):978-81

The efficacy of a garlic-ginkgo combination product (Allium plus) was
analyzed in a randomized placebo-controlled double-blind study under extreme
dietary conditions. The Christmas/New Year’s season was chosen for this 2
months lasting investigation analyzing whether the known cholesterol lowering
effect of garlic was even effective during the period of the year with the
most cholesterol-rich meals. 43 patients with elevated total cholesterol
levels ranging between 230- 390 mg/dl completed the study. There were no
significant changes of the total cholesterol values in both treatment groups.
Nevertheless the analysis of improvement or deterioration of total cholesterol
values revealed a clear difference between verum and placebo. 20% of the
patients in the placebo group showed an improvement of their total cholesterol
level, while there was a significant greater improvement rate of 35% in the
verum group (p < 0.05). The responders of the verum group showed a reduction in the total cholesterol values from 298.5 +/- 53.8 to 293.0 +/- 56.4 mg/dl after 1 month and a total reduction of 10.4% after 2 months to 267.6 +/- 44.4 mg/dl. The difference after 2 months of treatment was significantly different from the starting value (p < 0.05). After the 2 months treatment phase there was a 2 weeks wash-out period. During this period the total cholesterol value returned to 293.5 +/- 90.1 mg/dl showing the effectiveness of garlic treatment, but indicating the need for a continuous long-term therapy.

Kimbel KH

Ginkgo biloba [letter; comment]

In: Lancet (1992 Dec 12) 340(8833):1474

Kleijnen J Knipschild P

Ginkgo biloba [see comments]

In: Lancet (1992 Nov 7) 340(8828):1136-9

Kleijnen J Knipschild P

Ginkgo biloba for cerebral insufficiency.

In: Br J Clin Pharmacol (1992 Oct) 34(4):352-8

1. By means of a critical review we tried to establish whether there is
evidence from controlled trials in humans on the efficacy of Ginkgo biloba
extracts in cerebral insufficiency. 2. The methodological quality of 40 trials
on Ginkgo and cerebral insufficiency was assessed using a list of predefined
criteria of good methodology, and the outcome of the trials was interpreted in
relation to their quality. A comparison of the quality was made with trials of
co-dergocrine, which is registered for the same indication. 3. There were
eight well performed trials out of a total of 40. Shortcomings were limited
numbers of patients included, and incomplete description of randomization
procedures, patient characteristics, effect measurement and data presentation.
In no trial was double-blindness checked. Virtually all trials reported
positive results, in most trials the dosage was 120 mg Ginkgo extract a day,
given for at least 4-6 weeks. For the best trials, there were no marked
differences in the quality of the evidence of the efficacy of Ginkgo in
cerebral insufficiency compared with co-dergocrine. The results of the review
may be complicated by a combination of publication bias and other biases,
because there were no negative results reported in many trials of low
methodological quality. 4. Positive results have been reported for Ginkgo
biloba extracts in the treatment of cerebral insufficiency. The clinical
evidence is similar to that of a registered product which is prescribed for
the same indication. However, further studies should be conducted for a more
detailed assessment of the efficacy.

Kleijnen J Knipschild P

The comprehensiveness of Medline and Embase computer searches. Searches for
controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo
biloba for cerebral insufficiency and intermittent claudication.

In: Pharm Weekbl Sci (1992 Oct 16) 14(5):316-20

OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer
searches for controlled trials. DESIGN: Comparison of articles found after an
exhaustive search of the literature with the yield of a Medline or Embase
search. This was performed for controlled clinical trials on the efficacy of
three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo
biloba for intermittent claudication and cerebral insufficiency. The number of
controlled trials found by exhaustive search of the literature was 107, 61 and
45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the
proportion of all trials found by Medline was 17%, 36% and 31% respectively
and for Embase 13%, 25% and 58% respectively. After checking of the references
in the Medline articles 44%, 79% and 76% of all trials were identified. After
checking of the references in the Embase articles 42%, 72% and 93% of all
trials were identified. About 20% of the articles was not correctly indexed.
Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82%
and 92% of the best trials were identified through Embase. CONCLUSIONS: For
the topics mentioned, Medline and Embase searches are sufficient to get an
impression of the evidence from controlled trials, but only if references in
the articles are followed for further evidence. If one wants to get a more
complete picture, additional search strategies make sense. Of course, this
picture may be different for other topics.

Kobayashi N Suzuki R Koide C Suzuki T Matsuda H Kubo M

[Effect of leaves of Ginkgo biloba on hair regrowth in C3H strain
mice]

In: Yakugaku Zasshi (1993 Oct) 113(10):718-24 (Published in Japanese)

Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the
hair regrowth in normal and high butter diet-pretreated C3H strain mice which
posterior hair we shaved were investigated. GBE showed a promoting effect on
the hair regrowth. GBE had the inhibitory effects on blood platelet
aggregation, thrombin activity and fibrinolysis. GBE inhibited the increase of
serum the triglyceride level in high cholesterol diet-treated rats. These
results suggested that GBE promotes the hair regrowth and could be used as a
hair tonic.

Koltringer P Langsteger W Klima G Reisecker F Eber O

[Hemorheologic effects of ginkgo biloba extract EGb 761. Dose- dependent
effect of EGb 761 on microcirculation and viscoelasticity of blood]

In: Fortschr Med (1993 Apr 10) 111(10):170-2 (Published in German)

Method: In a randomized open clinical trial involving 42 patients with
pathological visco-elasticity values, the effect of a single intravenous
injection of 50, 100, 150 or 200 mg of the Ginkgo biloba extract EGb 761,
commercially available as Tebonin p.i. on the microcirculation of the skin
(Doppler flowmetry) and the visco- elasticity of whole blood was investigated.
Results: A dose-dependent significant increase in the microcirculation was
found. In the case of visco-elasticity, this dose-dependence was less marked.
The present study thus confirms the positive effect of EGb 761 on the
microcirculation and whole-blood visco-elasticity in patients with
pathological visco-elasticity values, already found in earlier studies, and
shows it to be dependent on the dose employed.

Krauskopf R., Guinot Ph., Peetz H.G.:

Long term on line EEG analysei de monstrating the pharmaco-dynamic effect of
a defined Ginkgo biloba extract.

In: Beaufour -Schwabe Internat. Report, 1983.

Kunkel H

EEG profile of three different extractions of Ginkgo biloba.

In: Neuropsychobiology (1993) 27(1):40-5

Two experiment were conducted to assess the electroencephalographic effects
of (1) three different dosages of a total extract of Ginkgo biloba (EGb 761,
Tebonin) and (2) three different extractions of G. biloba (Tebonin and two
fractions from it). The medicament was tested against placebo using a
double-blind cross-over design in 12 normal healthy males for each experiment.
Medication was administered for 3 days preceding the recording sessions. 25
parameters were computed from the EEG spectra. Medication-related effects were
obtained for most of the power measures, whereas dominant frequencies of the
respective frequency band remained largely unchanged. The differences between
the EEG effects of the two studies are critically discussed.

Lee K Ku JR Koh SD Kim KS

Effects of methanol extract of ginkgo biloba (EGb), its ethylacetate
fraction (EAF) and butanol fraction (BF) on the isolated aorta.

In: Jpn J Pharmacol (1992) 58 Suppl 2:377P

Long R Yin R Zhen Y

[Partial purification and analysis of allergenicity, immunogenicity of
Ginkgo biloba L. pollen]

In: Hua Hsi I Ko Ta Hsueh Hsueh Pao (1992 Sep) 23(4):429-32 (Published
in Chinese)

Pollens of Ginkgo biloba L. (G.b.l.p) have been found to be a kind of
important allergen which causes pollinosis in Chengdu. The goal of this study
is to purify G.b.l.p and to determine the allergenicity and immunogenicity of
various fractions. Crude extract was purified by gel filtration with Sephadex
G25, then G75. Two elution peaks were observed. On SDS-PAGE, the molecular
weights of protein of the 1st peak and the valley were 30-42 kd and 13-18kd,
respectively, and that of the 2nd peak was less than 13 kd. 40 patients with
allergic rhinitis and/or asthma underwent the skin test with crude extract and
various fractions of gel filtration; it revealed that the strongest allergenic
activity existed in the 1st peak and there was mild allergenic activity in the
2nd peak. The in vitro allergenic activity and immunogenic activity of various
fractions were examined by ELISA inhibition test. It was further confirmed
that the allergenic activity and immunogenic activity of the 1st peak were the
strongest, and those of the 2nd peak were the lowest. It is suggested that
diagnosing reagents can be made satisfactorily by partial purification, i.e.
discarding the inactive fractions, since allergenicity exists in various
fragments. But fractions of allergen with high IgG immunogenicity should be
selected to produce immunotherapy agents so as to enhance the production of
blocking antibody and thus improve the therapeutic effect.

Marcocci L Maguire JJ Droy-Lefaix MT Packer L

The nitric oxide-scavenging properties of Ginkgo biloba extract EGb
761.

In: Biochem Biophys Res Commun (1994 Jun 15) 201(2):748-55

Ginkgo biloba extract EGb 761 was found to be a scavenger of nitric oxide in
in vitro acellular systems, under physiological conditions. EGb 761 competed
with oxyhemoglobin for reaction with nitric oxide generated during the
interaction of hydroxylamine with Complex I of catalase. An EGb 761
dose-dependent decrease in the amount of nitrite formed in the reaction of
oxygen with nitric oxide produced from solution of 5 mM sodium nitroprusside
was also observed. These data implicate it as a potential therapeutic agent in
conditions of altered production of nitric oxide.

Olivier-J; Plath-P

Combined low power laser therapy and extracts of Ginkgo biloba in a blind
trial of treatment for tinnitus.

In: Laser Therapy (1993) 5(3): 137-139

Tinnitus is an annoying and often debilitating condition of neurootologic
origin but of uncertain aetiology. Many treatment methods have been tried, but
to date none has been consistently successful. The present preliminary study
presents a blind trial of laser therapy (c/w HeNe 632.8 nm and pulsed GaAs 904
nm) combined with doses of an extract of Ginkgo biloba (50 mg) in two groups of
20 patients, one experimental and one control. All 40 patients received the
biloba extract injection, but only the 20 experimental patients received real
laser irradiation, 8 days, 8 min per day. The control group received sham
irradiation in a blind arrangement. Fifty percent of the experimental group was
assessed to have a reduction in tinnitus of more than 10 dB, compared with 5%
in the control group in both self-assessment and audiometric findings. Although
only a preliminary report, the results are very encouraging, and the authors
suggest that this combined photochemotherapy is a promising treatment for
tinnitus.

Otani M Chatterjee SS Gabard B Kreutzberg GW

Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral
edema.

In: ACTA NEUROPATHOL (BERL) (1986) 69(1-2):54-65

The effect of an extract of Ginkgo biloba was studied on cerebral edema in
rats intoxicated with triethyltin chloride (TET). Brains of TET-treated rats
showed elevated water and sodium levels and a significant increase in the
sodium/potassium ratio. Animals treated with TET plus the extract did not show
water and electrolyte changes. The course of intoxication and treatment was
studied light- and electron-microscopically. A severe edema with extensive
vacuolization was seen in the cerebral and cerebellar white matter.
Morphometric measurements revealed a significant decrease in these
manifestations of the cytotoxic edema when the animals were treated with an
extract of Ginkgo biloba. Thus, we conclude that this extract has a protective
effect on the development of a cytotoxic edema in the white matter of the
brain.

Oyama Y Fuchs PA Katayama N Noda K

Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba
extract, greatly reduce oxidative metabolism in both resting and Ca(2+)-loaded
brain neurons.

In: Brain Res (1994 Jan 28) 635(1-2):125-9

The antioxidant action of myricetin and quercetin, the flavonoid constituents
of the extract of Ginkgo biloba (EGb), on oxidative metabolism of brain
neurons dissociated from the rats was examined using 2′, 7′-dichlorofluorescin
(DCFH) which is retained within the neuron and then is oxidized by cellular
hydrogen peroxide to be highly fluorescent. Incubation with myricetin or
quercetin reduced the oxidation of DCFH in resting brain neurons, more
profoundly than EGb. Myricetin decreased the oxidative metabolism at
concentrations of 3 nM or more. It was 10 nM or more for the case of
quercetin. Incubation with each flavonoid constituent also reduced the Ca(2+)-
induced increase in the oxidative metabolism without affecting the cellular
content of DCFH or the intracellular concentrations of Ca2+. Such an
antioxidant action of myricetin or quercetin may be responsible for a part of
the beneficial effects of EGb on brain neurons subject to ischemia.

Oyama Y Hayashi A Ueha T

Ca(2+)-induced increase in oxidative metabolism of dissociated mammalian
brain neurons: effect of extract of ginkgo biloba leaves.

In: Jpn J Pharmacol (1993 Apr) 61(4):367-70

Effect of an extract of Ginkgo biloba leaves (EGb) on oxidative metabolism
was studied using rat brain neurons and 2′, 7′- dichlorofluorescin
fluorescence. Ionomycin (100 nM to 1 microM), a Ca(2+)-ionophore,
dose-dependently augmented the 2′, 7′- dichlorofluorescin fluorescence in the
presence of external Ca2+, but not under the external Ca(2+)-free condition.
Preincubation of neurons with EGb (3 micrograms/ml) greatly reduced the
ionomycin- induced increase in 2′, 7′-dichlorofluorescin fluorescence. Results
suggest that EGb may reduce the Ca(2+)-induced increase in the oxidative
metabolism of brain neurons.

Oyama Y Ueha T Hayashi A Chikahisa L Noda K

Flow cytometric estimation of the effect of Ginkgo biloba extract on the
content of hydrogen peroxide in dissociated mammalian brain neurons.

In: Jpn J Pharmacol (1992 Dec) 60(4):385-8

The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide
was estimated in cerebellar neurons dissociated from rats, by means of a
flow-cytometer and 2′, 7′-dichlorofluorescein (DCF) diacetate, a fluorescent
dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF
fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further
increases in the GBE concentration (up to 3 micrograms/ml) produced a
dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces
the content of hydrogen peroxide or suppresses the reactive oxygen species
(ROS) formation of cerebellar neurons. The present technique may be useful for
preliminary evaluations of agents affecting the ROS formation in mammalian
brain neurons.

Petkov VD Kehayov R Belcheva S Konstantinova E Petkov VV Getova D
Markovska V

Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo
biloba (GK 501) and their combination Gincosan (PHL-00701).

In: Planta Med (1993 Apr) 59(2):106-14

In experiments on young (aged 3 months) and old (aged 26 months) rats, using
some conditioned-reflex methods with punishment or positive reinforcement for
active and passive avoidance (shuttle-box, step-down, step-through, and water
maze), we studied the effects of the standardized extracts of Panax ginseng
(G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The
extracts were administered orally for 7 days before training at three
increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for
GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their
combination improved the retention of learned behavior. This effect varied
considerably with the extracts, with the dose and with the behavioral method
used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba
GK501 extracts possess properties similar in every respect to those of
nootropic drugs. The favorable effects on learning and memory of the
combination of G115 plus GK501 and the other pharmacological activities
inherent in the extracts characterize this combination, offered as Gincosan as
a particularly promising drug in geriatric practice.

Pidoux B

[Effects of Ginkgo biloba extract on functional brain activity. An
assessment of clinical and experimental studies]

Effets sur l’activite fonctionnelle cerebrale de l’extrait de Ginkgo
biloba. Bilan d’etudes cliniques et experimentales.

In: Presse Med (1986 Sep 25) 15(31):1588-91

Electroencephalography is the only convenient method for functional
exploration of the brain and recent developments allows for pharmacological
studies of electoencephalograms. Using such techniques has confirmed those of
clinical trials, and notably the activity of Ginkgo on alertness.

Pidoux B., Bastien C., Niddam S.:

Clinical and quantitative EEG double-blind study of GBE.

In: J. Cerebral Blood Flow Metabolism, 1983, 3, 5556-5557.

Pidoux B., Bastien C., Niddam S.:

Normalization of electroencephalographic activity in ageing brain by an
extract of Ginkgo biloba;

In: Bes. A. Braquet P., Paoletti R., Siesjo B.K. Eds., Cerebral
Ischemia, Amsterdam, Excerpta Medica, 1984, 385-388.

Pietta P Mauri P Rava A

Rapid liquid chromatography of terpenes in Ginkgo biloba L. extracts and
products.

In: J Pharm Biomed Anal (1992 Oct-Dec) 10(10-12):1077-9

Pritz-Hohmeier S Chao TI Krenzlin J Reichenbach A

Effect of in vivo application of the ginkgo biloba extract EGb 761 (Rokan)
on the susceptibility of mammalian retinal cells to proteolytic enzymes.

In: Ophthalmic Res (1994) 26(2):80-6

Lesions, inflammations, or degenerative insults of the human retina are
accompanied by the release of proteolytic enzymes. Their deleterious effect
may be enhanced by the release of free radicals. Ginkgo biloba extracts are
known to exert protective influences against the action of free radicals, and
this prompted us to ask whether the application of such extracts might protect
retinal tissue against proteolytic damage. Eighteen adult rabbits were fed for
3 weeks (+/- 3 days) with 40 mg/kg of G. biloba extract (EGb 761) or a
terpene-free fraction of this extract, dissolved in their drinking water.
Twelve control rabbits received no G. biloba extract. The animals were then
euthanatized and their retinae isolated. After appropriate enzymatic
treatment, the tissue was dissociated and the number of isolated Muller cells
counted as an indication of the strength of the proteolytic effects. There was
a significant protective action of EGb 761: in an average control rabbit 5, 200
cells per milligram retinal tissue were isolated; application of EGb 761
markedly reduced this number to 2, 500 (terpene-free fraction; CP 205) or 3, 050
(terpene-containing fraction). It is concluded that G. biloba extracts may
have a significant therapeutic value in cases of retinal damage.

Racagni G Brunello N Paoletti R

[Neuromediator changes during cerebral aging. The effect of Ginkgo biloba
extract]

Variations des neuromediateurs lors du vieillissement cerebral. Effet de
l’extrait de Ginkgo biloba.

In: Presse Med (1986 Sep 25) 15(31):1488-90

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.

Ramassamy C Christen Y Clostre F Costentin J

The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5-
hydroxytryptamine: in-vitro and ex-vivo studies.

In: J Pharm Pharmacol (1992 Nov) 44(11):943-5

The Ginkgo biloba extract (EGb 761) added to a synaptosomal fraction prepared
from mice cerebral cortex modified [3H]5-hydroxytryptamine ([3H]5-HT) uptake
in a biphasic manner. Between 4 and 16 micrograms mL-1 EGb 761 increased
significantly the [3H]5-HT uptake (maximum + 23%). A similar increase was also
obtained when synaptosomes were prepared from the cortex of mice treated
orally with EGb 761, either acutely (100 mg kg-1, 14 h and 2 h before death)
or semi-chronically (2 x 100 mg-1 kg daily for 4 consecutive days). The
in-vitro increase in [3H]5-HT uptake induced by EGb 761 was not observed in
the presence of 10(-6) M clomipramine, a 5-HT-uptake inhibitor. EGb 761 did
not increase [3H]dopamine uptake by synaptosomes prepared from striatum of
mice. We investigated different fractions of EGb 761 in order to determine the
compounds inducing the increase in [3H]5-HT uptake. The BN 52063 extract
(corresponding to the EGb 761 devoid of flavonoid substances) did not increase
[3H]5-HT uptake. The Cp 202 extract (corresponding to the EGb 761 devoid of
terpenic substances and containing mostly flavonoid substances) increased
[3H]5-HT uptake. Among the flavonoids, quercetin has been tested and had no
effect on the [3H]5-HT uptake. Since at the usual therapeutic doses of EGb
761, the effective concentrations of the components responsible for this
increase are likely to be reached in the brain, one may suggest that this
effect could contribute to the therapeutic effect of EGb 761.

Ramassamy C Girbe F Christen Y Costentin J

Ginkgo biloba extract EGb 761 or trolox C prevent the ascorbi acid/Fe2+
induced decrease in synaptosomal membrane fluidity.

In: Free Radic Res Commun (1993) 19(5):341-50

The ability of synaptosomes, prepared from striata, to take up 3H- dopamine
declined rapidly during incubation at 37 degrees C, in an oxygenated
Krebs-Ringer medium with 0.1 mM ascorbic acid. Ascorbic acid was responsible
for this decrease. Its effectiveness after a 60 min incubation was
concentration dependent from 1 microM and virtually complete for 0.1 mM.
Furthermore, a decrease of synaptosomal membrane fluidity was revealed by
measurements of fluorescence polarization using 1, 6-diphenyl-1, 3, 5-hexatriene.
This decrease was potentiated by Fe2+ ions (1 microM). In contrast, it was
prevented by the Fe2+ ion chelator, desferrioxamine (0.1 mM), by the Ginkgo
biloba extract EGb 761 [2-16 micrograms/ml], as well as by the flavonoid
quercetin (0.1 microM). This preventive effect was shared by trolox C (from
0.1 mM). It is concluded that peroxidation of neuronal membrane lipids induced
by ascorbic acid/Fe2+ is associated with a decrease in membrane fluidity
which, in turn, reduces the ability of the dopamine transporter to take up
dopamine.

Ramassamy C Naudin B Christen Y Clostre F Costentin J

Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease
in synaptosomal dopamine or serotonin uptake following incubation.

In: Biochem Pharmacol (1992 Dec 15) 44(12):2395-401

Prolonged incubation of synaptosomes in Krebs-Ringer oxygenated medium in the
presence of ascorbic acid (10(-4) M) led, after 20 min, to a decrease in
[3H]dopamine (DA) (synaptosomes prepared from the striatum) and [3H]serotonin
(5HT) (synaptosomes prepared from the cortex) uptake. The decrease was
progressive and uptake was virtually abolished after a 60 min incubation
period. A concentration-dependent (from 5 x 10(-6) M) role of ascorbic acid in
the decrease of [3H]DA or [3H]5HT uptake was demonstrated. This decrease was
potentiated by Fe2+ ions and prevented by the ferrous chelating agent
desferrioxamine. Thus, the progressive decrease in synaptosomal uptake of
either [3H]DA or [3H]5HT could depend on the generation of free radicals by
the association of ascorbic acid with Fe2+ ions. The decrease in synaptosomal
uptake was prevented, in a concentration- dependent manner, by the Ginkgo
biloba extract EGb 761 (4-16 micrograms/mL) and the vitamin E analog trolox C
(10(-4) M). The terpenic fraction of EGb 761, Bn 52063 (up to 0.5
microgram/mL), did not prevent the reduction of [3H]amine uptake. In contrast,
the flavonoidic fraction, Cp 202, was effective (from 1 microgram/mL) and its
efficacy was shared by the flavonoid quercetin (from 0.1 microgram/mL). The
prolongation of the ability of synaptosomes to take up [3H]amine elicited by
EGb 761, in particular its

David L. Hoffmann BSc Hons MNIMH Written by David L. Hoffmann BSc Hons MNIMH

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