GINKGO BILOBA, ALZHEIMER AND SEXUAL DYSFUNCTION. / GINKGO BILOBA, ALZHEIMER Y DISFUNCION SEXUAL

 

Ginkgo Biloba,  Alzheimer, Sexual Dysfunction and others. ! 

 

Ginkgo Biloba, Alzheimer, Disfuncion Sexual y otras. !

 

 

 

EDITORIAL ENGLISH
 =================
Hi DERMAGIC friends, today with another interesting topic about another plant: THE GINKGO BILOBA, SEXUAL DYSFUNCTION, ALZHEIMER AND OTHERS. The GIKNGO or TREE OF MAIDENHAR, is of Chinese origin, has been found in fossils dating back 270 million years, and today is still considered a tremendous plant with great benefits for humanity.
 
Cultivated in many countries. Also known as the "SILVER APRICOT" whose erroneous Japanese translation gave rise to the name "GINKGO". Another name: THE TREE OF THE 40 SHIELDS "and is the only surviving tree of the Ginkgophyta species, all others are extinct.

The standard extract of dry leaves of Ginkgo biloba is called Egb 761 and contains 31.2% Ginkgo-flavonol glucosides, 15.4% terpene lactones, 6.94% bilobalide, 3.74% ginkgolide A, 1.62% ginkgolide B, 3.06% ginkgolid C, and 10.45 ppm ginkgolic acid, with broad spectrum of pharmacological activities.
 
One of its main effects is the ANTIPLATELET and ANTITHROMBOTIC effect, which has been successfully used in many conditions where it is necessary to improve the circulation, as in DIABETES, DIABETIC RETINOPATHY, SKIN GRAFT and INTERMITTENT CLAUDICATION.

Perhaps the most harmful adverse effect of GINKGO BILOBA is that the abuse in its dosage can cause HEMORRHAGES, mainly INTRACEREBRAL, SUBARACHNOIDAL AND OCULAR (HYPHEMA). So you should be careful not to co-administer it with warfarin or coumadin type anticoagulants.


If you review the references in detail you will find the multiple uses of the leaves of this tree, among which are highlighted lately NEUROVEGETATIVE DISEASES (ALZHEIMER), DEMENTIA, COGNITIVE DISORDERS AND MEMORY, Also in SEXUAL AND ERECTILE DYSFUNCTION, and other diseases like VITILIGO.

 SOME USES OF GINKGO BILOBA:
 =============================

 1.) PERIPHERAL AND CARDIOVASCULAR ISCHEMIA.
 2.) ANTIPLAQUETARY AND ANTITHROMBOTIC EFFECT.
 3) SEXUAL DYSFUNCTION.
 4.) NEURODEGENERATIVE DISEASES: ALZHEIMER.
 5.) TINNITUS.
 7.) INTERMITTENT CLAUDICATION.
 8.) RETINAL ALTERATIONS.
 9.) SKIN GRAFT
 10.) SOLAR PROTECTION (UVB) TOPICAL USE.
 11.) OXIDATIVE STRESS.
 12.) DIABETES (RETINOPATHY).
 13.) COGNITIVE DISORDERS AND DEMENTIA.
 13.) VITILIGO.
 14.) NEUROPROTECTIVE EFFECT.
 15.) GLAUCOMA.
 16.) COCHLEOVESTIBULARY PATHOLOGY.
 17.) LYMPHEDEMA.
 
You should also know that one of the main ingredients in Ginkgo biloba extract, QUERCETINE, is a known mutagen. Today, 2.017 studies are being carried out on GINKGO BILOBA and its potential carcinogenic effect in rats, and recently it has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer.

Group 2: products as probable carcinogenic to man. This group is subdivided into two:
2A high cancerous probability.
2B low cancerous probability. It is good that you know this information in case you are taking it.

In my experience, I do not know of any case that after using GINKGO BILOBA has developed any type of cancer. !
  
One of the aspects to be highlighted with GINKGO BILOBA is its use as NEUROPROTECTOR  in neurodegenerative diseases like ALZHEIMER, a disease in which an old antibiotic like MINOCYCLINE has also proven to be effective.

Ginkgo Biloba has also proven to be useful in the sexual aspect, improving ERECTILE DYSFUNCTION.


".... Once again MOTHER NATURE puts us on the way ancestral naturopathic medicines that improve our health .." GINKGO IS ANOTHER OF THEM ...

 In the 71 references the facts, in the attached the GINKGO BILOBA tree and its LEAVES.

 Greetings to all.

Dr. Jose Lapenta.



EDITORIAL ESPAÑOL
=================

Hola amigos DERMAGICOS, hoy con otro interesante tema sobre otra planta: EL GINKGO BILOBA, DISFUNCION SEXUAL, ALZHEIMER Y OTRAS. El GIKNGO o ARBOL DE MAIDENHAR, es de origen Chino, ha sido encontrado en fosiles con data de hace 270 millones de años, y hoy dia todavias es considerada tremenda planta con grandes beneficios para la humanidad.

Cultivado en muchos paises. Conocido tambien como el "ALBARICOQUE DE PLATA" de cuya traduccion erronea del japones dio origen al nombre de "GINKGO". Otro nombre: EL ARBOL DE LOS 40 ESCUDOS" y es el unico arbol sobreviviente de la especie división Ginkgophyta, todos los demás están extintos.

El extracto estandarizado de hojas secas de Ginkgo biloba es denominado Egb 761 y contiene

31,2 % de Ginkgo-flavonol glucósidos, 15,4% de lactonas terpénicas (6,94% de bilobalida, 3,74% de ginkgolida A, 1,62% de ginkgólido B, 3,06% de ginkgólido C) y 10,45 ppm de ácido ginkgólico, con amplio espectro de actividades farmacologicas.

Uno de sus principales efectos es el efecto ANTIPLAQUETARIO y ANTITROMBOTICO por lo cual ha sido utilizado con exito en numerosas afecciones donde se necesita mejorar la CIRCULACION, como en la DIABETES, RETINOPATIA DIABETICA, INJERTOS CUTANEOS y CLAUDICACION INTERMITENTE.  

Quiza el efecto adverso mas dañino del GINKGO BILOBA es que el abuso en su dosificacion puede provocar HEMORRAGIAS, principalmente INTRACEREBRALES, SUBARACNOIDEAS Y OCULARES (HIFEMA). De modo que debes tener cuidado de no co-administarlo con anticoagulantes tipo warfarina o coumadin.

Si revisas con detalle estas referencias te encontaras los multiples usos de las hojas de este arbol, entre las que destacan ultimamente ENFERMEDADES NEUROVEGETATIVAS (ALZHEIMER), DEMENCIA, TRASTORNOS COGNITIVOS Y MEMORIA, Tambien en la DISFUNCION SEXUAL, TRASTORNO DE LA ERECCION y otras enfermedades como VITILIGO.


ALGUNOS USOS DEL GINKGO BILOBA:
=============================

1.) ISQUEMIA PERIFERICA Y CARDIOVASCULAR.
2.) EFECTO ANTIPLAQUETARIO Y ANTITROMBOTICO.
3,) DISFUNCION SEXUAL.
4.) ENFERMEDADES NEURODEGENERATIVAS: ALZHEIMER.
5.) TINITUS.
7.) CLAUDICACION INTERMITENTE.
8.) ALTERACIONES RETINALES.
9.) INJERTOS CUTAEOS.
10.) PROTECCION SOLAR (UVB) USO TOPICO.
11.) ESTRES OXIDATIVO.
12.) DIABETES (RETINOPATIA).
13.) DEMENCIA Y TRASTRNOS COGNITIVOS.
13.) VITILIGO.
14.) NEUROPROTECTOR.
15.) GLAUCOMA.
16.) PATOLOGIA COCLEOVESTIBULAR.
17.) LINFEDEMA.  

Tambien debes conocer que uno de los ingredientes principales en el extracto de Ginkgo biloba, la QUERCETINA, es un mutagénico conocido. Hoy dia 2.017 se estan haciendo estudios del GINKGO BILOBA y su potencial efecto cancerigeno en ratas, y recientemente, ha sido clasificado como un posible carcinógeno humano (Grupo 2B) por la Agencia Internacional para la Investigación sobre el Cáncer. 

Grupo 2: productos como probables carcinógenos para el hombre. Este grupo se subdivide en dos: 2A alta probabilidad cancerígena.
2B baja probabilidad cancerígena. Es Bueno que conozcas esta informacion en caso de que lo estes tomando.

En mi experiancia no conozco ningun caso que luego de ingerir GINKGO BILOBA haya desarrolado algun tipo de cancer. ! 

Uno de los aspectos a destacar con el GINKGO BILOBA  es su uso como NEUROPROTECTOR en enfermedades neurodegenerativas coomo el ALZHEIMER, enfermedad en la que un viejo antibiotico como la MINOCICLINA tambien ha probado ser efectivo.

Tambien el Ginkgo Biloba ha demostrado ser util en el aspecto sexual, mejorando la DISFUNCION ERECTIL.

" ....Una vez mas la MADRE NATURALEZA nos pone en el camino medicinas naturistas ancestrales que mejoran nuestra salud .." EL GINKGO ES OTRA DE ELLAS... 

En las 71 referencias los hechos, en el adjunto el arbol GINKGO Y BILOBA y sus HOJAS.

Saludos a Todos.

Dr. Jose Lapenta.

================================================================
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
================================================================
1.) [Ginkgo biloba extract (EGb 761). State of knowledge in the dawn ofth eyear 2000]
2.)[Preparation and definition of Ginkgo biloba extract].
3.) Subarachnoid haemorrhage associated with Ginkgo biloba.
4.) Extracts of Ginkgo biloba and bleeding or haemorrhage.
5.) Association of Ginkgo biloba with intracerebral hemorrhage.
6.) Spontaneous hyphema associated with ingestion of Ginkgo biloba extract.
7.) Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion.
8.) Antiplatelet and antithrombotic effects of a combination of ticlopidine and ginkgo biloba ext (EGb 761).
9.) [Paroxysmal non-hereditary angioedema].
10.)Dietary supplement-drug interactions.
11.)Herbal remedies: adverse effects and drug interactions.
12.)Herbal medicinals: selected clinical considerations focusing on knownor potential drug-herb interactions.
13.)The protective effect of Ginkgo biloba extract on CCl4-induced hepaticdamage.
14.)Ginkgo biloba for antidepressant-induced sexual dysfunction.
15.)The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.
16.) Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy.
17.)Free radicals in Alzheimer's dementia: currently available therapeuticstrategies.
18.)Proof of efficacy of the ginkgo biloba special extract EGb 761 inoutpatients suffering  from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.
19.)The relevance of herbal treatments for psychiatric practice.
20.)[The effect of gingko biloba on cochleovestibulary pathology of vascular origin].
21.)Effects of Ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs.
22.)Ginkgo biloba for tinnitus: a review.
23.)[Contribution of a combination of alpha and beta benzopyrones,flavonoidsand natural terpenes in the treatment of lymphedema of the lower limbs at the
2d stage of the surgical classification].
24.)[Gingko biloba extract EGb 761 and pentoxifylline in intermitten claudication. Secondary analysis of the clinical effectiveness].
25.)[Placebo-controlled double-blind study of the effectiveness of Ginkgo biloba special  extract EGb 761 in trained patients with intermittent claudication]
26.)[Ginkgo biloba in treatment of intermittent claudication. A systematic research based on controlled studies in the literature]
27.)Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal alterations.
28.)Ginkgo biloba extract increases ocular blood flow velocity.
29.)Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1,3-glucan formulation appears to inhibit the elicitation of allergic contact dermatitis in man.
30.)The effect of Gingko biloba extract (Egb 761) as a free radical scavenger on the survival of skin flaps in rats. A comparative study.
31.)Induction of superoxide dismutase and catalase activity in different rattissues and protection from UVB irradiation after topical application of Ginkgo biloba extracts.
32.)In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides.
33.)Reactive oxygen metabolites, antioxidants and head and neck cancer.
34.)Protective effects of Gingko biloba extract EGb 761 on myocardium of experimentally diabetic rats. I: ultrastructural and biochemical investigation on cardiomyocytes.
45.)Identification of Gingko biloba flavonol metabolites after oral administration to humans.
46.)Solid-phase extraction and gas chromatography-mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets.
47.)Ginkgo biloba extract (EGb 761) independently improves changes in passive  avoidance learning and brain membrane fluidity in the aging mouse.
48.)Lipid peroxidation in experimental spinal cord injury. Comparison of treatment with Ginkgo biloba, TRH and methylprednisolone.
49.)A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress.
50.)The correlation of cytophotometrically and biochemically measured enzyme activities: changes in the myocardium of diabetic and hypoxic diabetic rats, with and without Ginkgo biloba extract treatment.
51.)Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma.
52.)Platelet-activating factor is an important mediator in hypoxic ischemic brain injury in the newborn rat. Flunarizine and Ginkgo biloba extract reduce PAF concentration in the brain.
53.)The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid peroxide, some free radical scavengers and the cardiovascular system of aged rats.
54.)Effects on skeletal muscle fibres of diabetes and Ginkgo biloba extract treatment.
55.)The effects of prostaglandin E2 indomethacin & Ginkgo biloba extract on resistance to experimental sepsis.
56.)Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide.
57.) Potential benefits of phytochemicals against Alzheimer's disease.
58.) An Overview of Systematic Reviews of Ginkgo biloba Extracts for Mild Cognitive Impairment and Dementia.
59.) Effects of Ginkgo biloba on dementia: An overview of systematic reviews.
60.) Ginkgo biloba for cognitive impairment and dementia.
61.) Effects of Ginkgo biloba on dementia: An overview of systematic reviews.
62.) Triple-blind, placebo-controlled trial of Ginkgo biloba in sexual dysfunction due to
63.) Alternative Systemic Treatments for Vitiligo: A Review.
64.) Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial.
65.) Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system.
66.) Effect of Ginkgo biloba Extract (EGb-761) on Recovery of Erectile Dysfunction in Bilateral Cavernous Nerve Injury Rat Model.
67.) A Urologist's Guide to Ingredients Found in Top-Selling Nutraceuticals for Men's Sexual Health.
68.) Triple-blind, placebo-controlled trial of Ginkgo biloba in sexual dysfunction due to antidepressant drugs.
69.) Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 Jun;36(6):674-7.
[Treatment of Early Diabetic Retinopathy by Liuwei Dihuang Pill Combined Ginkao Leaf Tablet].
70.) Neuroprotection in Glaucoma.
71.) Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports.
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1.) [Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of
the year 2000]
===========================================================
Author
Clostre F
Address
Institut Henri Beaufour, Les Ulis.
Source
Ann Pharm Fr, 57 Suppl 1():1S8-88 1999 Jul

EGb 761 is a standardized extract of dried leaves of Ginkgo biloba
containing 24%
ginkgo-flavonol glycosides, 6% terpene lactones such as ginkgolides A,
B, C, J and
bilobalide. Its broad spectrum of pharmacological activities allows it
to be in adequacy to the
numerous pathological requirements--hemodynamic, hemorheological,
metabolic--which
occur in cerebral, retinal, cochleovestibular, cardiac or peripheral
ischemia. Moreover, EGb
761 has direct effects against necrosis and apoptosis of neurons and
improves neural plasticity
as evidenced in vestibular compensation. At the molecular and the
cellular levels, some
evidence obtained with animal models indicates that EGb 761 can
interact as a free
radical-scavenger and a inhibitor of lipid peroxidation with all, or
nearly all reactive oxygen
species; maintains ATP content by a protection of mitochondrial
respiration and preservation
of oxidative phosphorylations; exerts arterial and venous
vasoregulator effects involving the
release of endothelial factors and the catecholaminergic system.
Moreover, EGb 761
regulates ionic balance in damaged cells and exerts a specific and
potent Platelet-activating
factor antagonist activity. Numerous well-controlled clinical studies,
realized in Europe and in
USA, have revealed that EGb 761 is an effective therapy for a wide
variety of disturbances of
cerebral function, ranging from cerebral impairment of ischemic
vascular origins (i.e. multi
infarct dementia), early cognitive decline to mild-to-moderate cases
of the more severe types
of senile dementias (including Alzheimer's disease) or mixed origins
(i.e. psychoorganic origin).
Improvement of signs and symptoms have been demonstrated for cognitive
functions,
particularly for memory loss, attention, alertness, vigilance, arousal
and mental fluidity. Some
clinical studies have showed that EGb 761 treatment may improve the
capacity of geriatric
patients to cope with the stressful demands of daily life. The
explanation is a dual
stress-alleviating action of EGb 761: its facilitates behavioral
adaptation to stress and may
decrease the excess of cortisol release to stress. Moreover, EGb 761
shows a specific
neuroprotective effects to hippocampic cells. Regarding the visual
system, experimental
studies have shown that EGb 761 can inhibit or reduce the functional
retinal impairments
resulting from ischemia-reperfusion, photo-degeneration, diabetic or
proliferative retinopathy.
Clinical studies have revealed that EGb 761 may be useful in treating
visual activity
impairments and damages to the visual field associated with chronic
cerebrovascular
insufficiency, senile macular degeneration and diabete mellitus.
Regarding the vestibular and
auditory systems, experimental and clinical studies have shown the
efficacy of EGb 761 in
treating hypoacusis, tinnitus, vertigo, dizziness and other symptoms
of vestibulocochlear
disorders. At least, adequatly controlled studies in patients with
peripheral arterial occlusive
disease have provided good evidence for therapeutic efficacy in
intermittent claudication. The
future of EGb 761 is undoubtedly in the promise in slowing the
progression of Alzheimer's
disease. Indeed, two recent american clinical studies have shown the
efficacy and safety of
EGb 761 in patients with mild to severe Alzheimer's disease and
multi-infarct dementia. In
clinical terms, progression of symptoms was delayed by approximately 6
months. Actually
new clinical studies are undertaken in USA and Europe. At the dawn of
the third millenium
(the Sixth for Ginkgo biloba) we propose a state of art about it.

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2.)[Preparation and definition of Ginkgo biloba extract].
===========================================================
Presse Med 1986 Sep 25;15(31):1455-7

Drieu K
Ginkgo biloba extract is a well-defined and complex product prepared from
green leaves of Ginkgo biloba. The leaves are harvested from trees growing
in plantations in South Corea, Japan and France. The mode of culture,
harvesting and extraction are perfectly standardized and controlled.
Analysis of Ginkgo biloba extract makes it possible to confirm that
undesirable substances have been eliminated and to measure the amount of
active principles. The extract contains flavonoid substances, such as the
Ginkgo-flavone glycosides and terponoids which are characteristic of Ginkgo
and have a unique structure (ginkgolides, bilobalide).

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3.) Subarachnoid haemorrhage associated with Ginkgo biloba.
===========================================================
Lancet 1998 Jul 4;352(9121):36

Vale S
Letter
===========================================================
4.) Extracts of Ginkgo biloba and bleeding or haemorrhage.
===========================================================
Lancet 1998 Oct 3;352(9134):1145-6

Skogh M
Publication Types:
Letter
===========================================================
5.) Association of Ginkgo biloba with intracerebral hemorrhage.
===========================================================
Neurology 1998 Jun;50(6):1933-4

Matthews MK Jr
Publication Types:
Letter
===========================================================
6.) Spontaneous hyphema associated with ingestion of Ginkgo biloba extract.
===========================================================
N Engl J Med 1997 Apr 10;336(15):1108

Rosenblatt M, Mindel J
Publication Types:
Letter
===========================================================
7.) Spontaneous bilateral subdural hematomas associated with chronic Ginkgo
biloba ingestion.
===========================================================
Neurology 1996 Jun;46(6):1775-6

Rowin J, Lewis SL
Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical
Center, Chicago, IL 60612, USA.

Comment in: Neurology 1997 Mar;48(3):789-90
Comment in: Neurology 1997 Apr;48(4):1137
Comment in: Neurology 1998 Jun;50(6):1933-4
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8.) Antiplatelet and antithrombotic effects of a combination of ticlopidine
and ginkgo
biloba ext (EGb 761).
===========================================================
Thromb Res 1998 Jul 1;91(1):33-8

Kim YS, Pyo MK, Park KM, Park PH, Hahn BS, Wu SJ, Yun-Choi HS
Natural Products Research Institute, Seoul National University, Korea.

The antiplatelet and antithrombotic effects of the oral combination
treatment of ticlopidine and Ginkgo biloba extract (EGb 761) were studied
in normal and thrombosis-induced rats. The ex vivo inhibitory effect on
ADP-induced platelet aggregation of a small dose of ticlopidine (50
mg/kg/day) in combination with EGb 761 (40 mg/kg/day) was comparable to a
larger dose of only ticlopidine (200 mg/kg/day). Bleeding time was also
prolonged by 150%. Thrombus weight was also consistently decreased by a
combination of ticlopidine and EGb 761 in an arterio-venous shunt model at
two doses of ticlopidine (50 mg/kg) plus EGb 761 (20 mg/kg) and ticlopidine
(50 mg/kg) plus EGb 761 (40 mg/kg). A combinatory treatment in acute
thrombosis model in mice also showed a higher recovery than a single
treatment.

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9.) [Paroxysmal non-hereditary angioedema].
===========================================================
Dtsch Med Wochenschr 1990 Oct 19;115(42):1586-90
[Article in German]

Steurer J, Siegenthaler-Zuber G, Siegenthaler W, Suter S, Kessler FJ,
Vahlensieck M, Streuli R, Lingg G
Departement fur Innere Medizin, Universitatsspital Zurich.

Recurrent hypovolaemic shock had been occurring over the last five and four
years, respectively, in a 53-year-old woman and a 46-year-old man who had
previously been healthy. The attacks were characterized by a tension
feeling and sometimes oedema in the limbs, as well as increased thirst.
Within a few hours sweating, tachycardia, orthostatic complaints and shock
would occur. The woman's systolic blood pressure would fall to 70 mm Hg and
the pulse rate rise to 150/min. The man's blood pressure was not measurable
by sphygmomanometer during his first attack. Haematocrit rose to 61 and
71.5%, haemoglobin concentration to 20.7 and 21.3 g/dl, respectively. On
administration of plasma expanders all abnormal clinical and biochemical
changes quickly disappeared, only to recur within weeks or months. The
cause of the condition is an increased permeability of the tissue
capillaries, while renal, pulmonary and cerebral vessels apparently are
unaffected. During ketotifen and tebonin (gingko biloba extract)
administration to the man, he required no further hospitalization for nine
months, after which he had three severe attacks. The woman had a severe
attack of hypovolaemic shock one month on this treatment. The prognosis of
capillary leak syndrome is bad.

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10.)Dietary supplement-drug interactions.
===========================================================
J Am Med Womens Assoc 1999 Fall;54(4):191-2

Smolinske SC
Children's Hospital of Michigan Regional Poison Control Center, USA.

Recent surveys show that 18% of adults in the United States use
prescription drugs concurrently with herbal or vitamin products, placing an
estimated 15 million patients at risk of potential drug-supplement
interactions. Despite this widespread concurrent use of conventional and
alternative medicines, documented drug-herb interactions are sparse. This
review focuses on possible interactions between drugs and herbal medicines
used for phytoestrogen-hormone and antiplatelet-oral anticoagulant therapy.
Interactions with phytoestrogens are purely speculative, based on
competitive estrogen-receptor binding or antiestrogenic effects. In
contrast, several case reports document bleeding complications with Ginkgo
biloba, with or without concomitant drug therapy. Case reports are also
suggestive of interaction between warfarin and dong quai or Panax ginseng.
Recommendations for counseling patients at highest risk of adverse
interactions are given.

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11.)Herbal remedies: adverse effects and drug interactions.
===========================================================
Am Fam Physician 1999 Mar 1;59(5):1239-45

Cupp MJ
Drug Information Center, West Virginia University School of Pharmacy,
Morgantown 26506-9550, USA.

A growing number of Americans are using herbal products for preventive and
therapeutic purposes. The manufacturers of these products are not required
to submit proof of safety and efficacy to the U.S. Food and Drug
Administration before marketing. For this reason, the adverse effects and
drug interactions associated with herbal remedies are largely unknown.
Ginkgo biloba extract, advertised as improving cognitive functioning, has
been reported to cause spontaneous bleeding, and it may interact with
anticoagulants and antiplatelet agents. St. John's wort, promoted as a
treatment for depression, may have monoamine oxidase-inhibiting effects or
may cause increased levels of serotonin, dopamine and norepinephrine.
Although St. John's wort probably does not interact with foods that contain
tyramine, it should not be used with prescription antidepressants.
Ephedrine-containing herbal products have been associated with adverse
cardiovascular events, seizures and even death. Ginseng, widely used for
its purported physical and mental effects, is generally well tolerated, but
it has been implicated as a cause of decreased response to warfarin.
Physicians must be alert for adverse effects and drug interactions
associated with herbal remedies, and they should ask all patients about the
use of these products.

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12.)Herbal medicinals: selected clinical considerations focusing on known or
potential drug-herb interactions.
===========================================================

Arch Intern Med 1998 Nov 9;158(20):2200-11

Miller LG
Department of Pharmacy Practice, Texas Tech University Health Sciences
Center, Amarillo 79121, USA.

Herbal medicinals are being used by an increasing number of patients who
typically do not advise their clinicians of concomitant use. Known or
potential drug-herb interactions exist and should be screened for. If used
beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should
not be used with other known hepatoxic drugs, such as anabolic steroids,
amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the
1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine
alkaloids. Nonsteroidal anti-inflammatory drugs may negate the usefulness
of feverfew in the treatment of migraine headaches. Feverfew, garlic,
Ginkgo, ginger, and ginseng may alter bleeding time and should not be used
concomitantly with warfarin sodium. Additionally, ginseng may cause
headache, tremulousness, and manic episodes in patients treated with
phenelzine sulfate. Ginseng should also not be used with estrogens or
corticosteroids because of possible additive effects. Since the mechanism
of action of St John wort is uncertain, concomitant use with monoamine
oxidase inhibitors and selective serotonin reuptake inhibitors is ill
advised. Valerian should not be used concomitantly with barbiturates
because excessive sedation may occur. Kyushin, licorice, plantain, uzara
root, hawthorn, and ginseng may interfere with either digoxin
pharmacodynamically or with digoxin monitoring. Evening primrose oil and
borage should not be used with anticonvulsants because they may lower the
seizure threshold. Shankapulshpi, an Ayurvedic preparation, may decrease
phenytoin levels as well as diminish drug efficacy. Kava when used with
alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc)
should not be given with immunosuppressants (eg, corticosteroids and
cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw
palmetto) may inhibit the absorption of iron. Kelp as a source of iodine
may interfere with thyroid replacement therapies. Licorice can offset the
pharmacological effect of spironolactone. Numerous herbs (eg, karela and
ginseng) may affect blood glucose levels and should not be used in patients
with diabetes mellitus.

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13.)The protective effect of Ginkgo biloba extract on CCl4-induced hepatic
damage.
===========================================================
Author
Ozenirler S; Din¸cer S; Akyol G; Ozo¨gul C; Oz E
Address
Department of Gastroenterology, Gazi University Faculty of Medicine,
Be¸sevler, Ankara,
Turkey.
Source
Acta Physiol Hung, 85(3):277-85 1997-98
Abstract
The aim of this study was to evaluate the protective effect of Ginkgo
biloba extract on
CCl4-induced hepatic damage in rats. Hepatic malondialdehyde,
glutathione and
hydroxyproline levels and histopathologic alterations in liver
specimens were assessed. 200
mg/kg/day Ginkgo biloba extract were given orally to the animals for
10 days, then a single
dose of 2 ml/kg b.w. carbon tetrachloride was, administered
intraperitoneally. Ginkgo biloba
extract treatment reduced hepatic malondialdehyde levels significantly
(p < 0.05), but did not
alter glutathione (p > 0.05) and hydroxyproline levels (p > 0.05). The
light and electron
microscopic findings showed that Ginkgo biloba extract limited the
CCl4-induced hepatocyte
necrosis and atrophy. These results suggest that this extract may
protect the hepatocytes from
carbon tetrachloride-induced liver injury.

===========================================================
14.)Ginkgo biloba for antidepressant-induced sexual dysfunction.
Author
===========================================================
Cohen AJ; Bartlik B
Address
University of California, San Francisco, California, USA.
Source
J Sex Marital Ther, 24(2):139-43 1998 Apr-Jun
Abstract
In an open trial ginkgo biloba, an extract derived from the leaf of
the Chinese ginkgo tree and
noted for its cerebral enhancing effects, was found to be 84%
effective in treating
antidepressant-induced sexual dysfunction predominately caused by
selective serotonin
reuptake inhibitors (SSRIs, N = 63). Women (n = 33) were more
responsive to the sexually
enhancing effects of ginkgo biloba than men (N = 30), with relative
success rates of 91%
versus 76%. Ginkgo biloba generally had a positive effect on all 4
phases of the sexual
response cycle: desire, excitement (erection and lubrication), orgasm,
and resolution
(afterglow). This study originated from the observation that a
geriatric patient on ginkgo
biloba for memory enhancement noted improved erections. Patients
exhibited sexual
dysfunction secondary to a variety of antidepressant medications
including selective serotonin
reuptake inhibitor (SSRIs), serotonin and nonrepinephrine reuptake
inhibitor (SNRIs)
monoamine oxidase inhibitor (MAOIs), and tricyclics. Dosages of ginkgo
biloba extract
ranged from 60 mg qd to 120 mg bid (average = 209mg/d). The common
side effects were
gastrointestinal disturbances, headache, and general central nervous
system activation. The
article includes a discussion of presumed pharmacologic mechanisms,
including effects on
platelet activating factor, prostaglandins, peripheral vasodilatation,
and central serotonin and
norepinephrine receptor factor modulation.

===========================================================
15.)The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.
===========================================================
Arch Neurol 1998 Nov;55(11):1409-15

Oken BS, Storzbach DM, Kaye JA
Department of Neurology, Oregon Health Sciences University, Portland 97201,
USA. oken@ohsu.edu

OBJECTIVE: To determine the effect of treatment with Ginkgo biloba extract
on objective measures of cognitive function in patients with Alzheimer
disease (AD) based on formal review of the current literature. METHODS: An
attempt was made to identify all English and non-English-language articles
in which G. biloba extract was given to subjects with dementia or cognitive
impairment. Inclusion criteria for the meta-analysis were (1) sufficiently
characterized patients such that it was clearly stated there was a
diagnosis of AD by either Diagnostic and Statistical Manual of Mental
Disorders, Revised Third Edition, or National Institute of Neurological
Disorders and Stroke-Alzheimer's Disease and Related Disorders Association
criteria, or there was enough clinical detail to determine this by our
review; (2) clearly stated study exclusion criteria, ie, those studies that
did not have stated exclusions for depression, other neurologic disease,
and central nervous system-active medications were excluded; (3) use of
standardized ginkgo extract in any stated dose; (4) randomized,
placebo-controlled and double-blind study design; (5) at least 1 outcome
measure was an objective assessment of cognitive function; and (6)
sufficient statistical information to allow for meta-analysis. RESULTS: Of
more than 50 articles identified, the overwhelming majority did not meet
inclusion criteria, primarily because of lack of clear diagnoses of
dementia and AD. Only 4 studies met all inclusion criteria. In total there
were 212 subjects in each of the placebo and ginkgo treatment groups.
Overall there was a significant effect size of 0.40 (P<.0001). This modest
effect size translated into a 3% difference in the Alzheimer Disease
Assessment Scale-cognitive subtest. CONCLUSIONS: Based on a quantitative
analysis of the literature there is a small but significant effect of 3- to
6-month treatment with 120 to 240 mg of G. biloba extract on objective
measures of cognitive function in AD. The drug has not had significant
adverse effects in formal clinical trials but there are 2 case reports of
bleeding complications. In AD, there are limited and inconsistent data that
preclude determining if there are effects on noncognitive behavioral and
functional measures as well as on clinician's global rating scales. Further
research in the area will need to determine if there are functional
improvements and to determine the best dosage. Additional research will be
needed to define which ingredients in the ginkgo extract are producing its
effect in individuals with AD.

===========================================================
16.) Medicinal plants and Alzheimer's disease: from ethnobotany to
phytotherapy.
===========================================================
J Pharm Pharmacol 1999 May;51(5):527-34

Perry EK, Pickering AT, Wang WW, Houghton PJ, Perry NS
Medical Research Council, Newcastle General Hospital, Newcastle upon Tyne.
e.k.perry@ncl.ac.uk

The use of complementary medicines, such as plant extracts, in dementia
therapy varies according to the different cultural traditions. In orthodox
Western medicine, contrasting with that in China and the Far East for
example, pharmacological properties of traditional cognitive- or
memory-enhancing plants have not been widely investigated in the context of
current models of Alzheimer's disease. An exception is Gingko biloba in
which the gingkolides have antioxidant, neuroprotective and cholinergic
activities relevant to Alzheimer's disease mechanisms. The therapeutic
efficacy of Ginkgo extracts in Alzheimer's disease in placebo controlled
clinical trials is reportedly similar to currently prescribed drugs such as
tacrine or donepezil and, importantly, undesirable side effects of Gingko
are minimal. Old European reference books, such as those on medicinal
herbs, document a variety of other plants such as Salvia officinalis (sage)
and Melissa officinalis (balm) with memory-improving properties, and
cholinergic activities have recently been identified in extracts of these
plants. Precedents for modern discovery of clinically relevant
pharmacological activity in plants with long-established medicinal use
include, for example, the interaction of alkaloid opioids in Papaver
somniferum (opium poppy) with endogenous opiate receptors in the brain.
With recent major advances in understanding the neurobiology of Alzheimer's
disease, and as yet limited efficacy of so-called rationally designed
therapies, it may be timely to re-explore historical archives for new
directions in drug development. This article considers not only the value
of an integrative traditional and modern scientific approach to developing
new treatments for dementia, but also in the understanding of disease
mechanisms. Long before the current biologically-based hypothesis of
cholinergic derangement in Alzheimer' s disease emerged, plants now known
to contain cholinergic antagonists were recorded for their amnesia- and
dementia-inducing properties.

===========================================================
17.)Free radicals in Alzheimer's dementia: currently available therapeutic
strategies.
===========================================================
J Neural Transm Suppl 1998;54:211-9

Rosler M, Retz W, Thome J, Riederer P
Psychiatric Department, University of Wurzburg, Federal Republic of Germany.

Substantial evidence now exists that oxidative stress may play an important
role in the etiopathogenesis of DAT. The different sources of oxidative
stress in DAT are suggesting several pharmacological opportunities for
influencing the disease. It is possible to distinguish 2 major types of
possible therapeutic agents according to their pharmacological point of
attack. 1. Radical scavengers, agents directly interacting with free
radicals. Candidates of this type are gingko biloba, vitamins A, C, E and
estrogen. 2. Antioxidants, which are able to prevent or decrease the
production of free radicals by use of specific neuropharmacological
properties. Candidates are selegiline, a MAO-B inhibitor well established
in the therapy of Parkinson's disease, and tenilsetam, which is believed to
be an AGE-inhibitor. Recent in vitro studies have demonstrated the efficacy
of both types of therapeutic agents by preventing or delaying oxidative
neural damage. Some clinical data exist regarding the antidementive
properties particularly in terms of gingko biloba, selegiline and vitamin
E. The efficacy studies about these compounds seem to indicate a promising
future strategy in the therapy of DAT. But it is too early to draw definite
conclusions since it is well known that all of our candidate substances do
not act specifically as radical scavengers or antioxidants.


===========================================================
18.)Proof of efficacy of the ginkgo biloba special extract EGb 761 in
outpatients suffering from mild to moderate primary degenerative dementia
of the Alzheimer type or multi-infarct dementia.
===========================================================
Author
Kanowski S; Herrmann WM; Stephan K; Wierich W; H¨orr R
Address
Department of Gerontopsychiatry, Free University Berlin, Germany.
Source
Pharmacopsychiatry, 29(2):47-56 1996 Mar
Abstract
The efficacy of the ginkgo biloba special extract EGb 761 in outpatients
with presenile and senile primary degenerative dementia of the Alzheimer
type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was
investigated in a prospective, randomized, double-blind,
placebo-controlled, multi-center study. After a 4-week run-in period, 216
patients were included in the randomized 24-week treatment period. These
received either a daily oral dose of 240 mg EGb 761 or placebo. In
accordance with the recommended multi-dimensional evaluation approach,
three primary variables were chosen: the Clinical Global Impressions (CGI
Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for
the assessment of the patient's attention and memory, and the N¨urnberger
Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of
daily life. Clinical efficacy was assessed by means of a responder
analysis, with therapy response being defined as response in at least two
of the three primary variables. The data from the 156 patients who
completed the study in accordance with the study protocol were taken into
account in the confirmatory analysis of valid cases. The frequency of
therapy responders in the two treatment groups differed significantly in
favor of EGb 761, with p < 0.005 in Fisher's Exact Test. The
intent-to-treat analysis of 205 patients led to similar efficacy results.
Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in
dementia of the Alzheimer type and multi-infarct dementia was confirmed.
The investigational drug was found to be well tolerated.

===========================================================
19.)The relevance of herbal treatments for psychiatric practice.
===========================================================
Aust N Z J Psychiatry 1999 Aug;33(4):482-9; discussion 490-3

Walter G, Rey JM
Department of Psychological Medicine, University of Sydney, New South
Wales, Australia. gwalter@mail.usyd.edu.au

OBJECTIVE: The aim of this paper is to inform psychiatrists about the basic
priniciples, terminology, schools of thought, efficacy, safety and
regulatory issues regarding herbal treatments for mental illness. METHOD:
Information was obtained by computerised and manual searching of medical
and botanical data bases, and by discussions with experts in herbal
medicine and regulatory aspects of the pharmaceutical industry. RESULTS:
Herbal medicines are commonly used in developed and developing countries
for psychiatric illness. The main schools of herbal medicine in Australia
are Western herbal medicine, traditional Chinese medicine and 'Ayurveda'
(Indian herbal medicine). Herbs used for psychiatric or neurological
disorders are termed 'nervines'. Three nervines which have attracted
considerable attention recently are St John's Wort, Gingko biloba and
Valeriana officinalis. In Australia, most herbal drugs are classed as
'listed drugs' which are required to satisfy less rigorous safety and
efficacy criteria than 'registered drugs'. The popularity of herbal
remedies has a number of clinical and research implications for psychiatry.
CONCLUSIONS: Psychiatrists should not endorse treatments that are
unsupported by sound research, nor remain ignorant about alternative
approaches to mental illness. The extent of use of herbal treatments for
mental illness suggests that psychiatrists should become more knowledgeable
about developments in this area.

===========================================================
20.)[The effect of gingko biloba on cochleovestibulary pathology of vascular
origin].
===========================================================
An Otorrinolaringol Ibero Am 1995;22(6):619-29
[Article in Spanish]

Cano Cuenca B, Marco Algarra J, Perez del Valle B, Pellicer Pascual FJ

The AA. of the present paper recall the clinical and functional results of
this therapy in a group of 70 patients complaining of vertigo. The Gingko
biloba extract (4 ml/12 h per mouth) has been continued during 6 months.
Neck and vertebrobasilar insufficiency were predominant causes. Six months
later statistically significant changes regarding the decrease of intensity
of tinnitus and vertigo crises were confirmed. Besides favorable
alterations in the peripherical symptomatology as a relative hearing
improvement turned up.

===========================================================
21.)Effects of Ginkgo biloba extract on the cochlear damage induced by local
gentamicin installation in guinea pigs.
===========================================================
Author
Jung HW; Chang SO; Kim CS; Rhee CS; Lim DH
Address
Department of Otorhinolaryngology - Head & Neck Surgery, Seoul National
University College of Medicine, Korea.
Source
J Korean Med Sci, 13(5):525-8 1998 Oct
Abstract
Investigations evaluating the protective effect of Ginkgo biloba extract
(EGb) on gentamicin (GM) ototoxicity were undertaken. Guinea pigs treated
with 5 mg/kg gentamicin sulfate on the round window niche (RWN) showed
acute changes on electrocochleogram and hair cell or microvilli damage on
scanning electron microscopy (SEM). There was accumulation of GM in the
whole cochlea, especially in the organ of Corti, stria vascularis, and type
III fibrocyte on immunohistochemical study. However, the guinea pigs
pretreated with local or systemic EGb revealed no significant changes by
local GM installation. From these results, we concluded that EGb has a
protective effect on the development of GM ototoxicity in the cochlea.
Language

===========================================================
22.)Ginkgo biloba for tinnitus: a review.
===========================================================
Clin Otolaryngol 1999 Jun;24(3):164-7

Ernst E, Stevinson C
Department of Complementary Medicine, School of Postgraduate Medicine and
Health Sciences, University of Exeter, UK. E.Ernst@exeter.ac.uk
===========================================================
===========================================================
23.)[Contribution of a combination of alpha and beta benzopyrones, flavonoids
and natural terpenes in the treatment of lymphedema of the lower limbs at
the 2d stage of the surgical classification].
===========================================================
Minerva Cardioangiol 1996 Sep;44(9):447-55
[Article in Italian]

Vettorello G, Cerreta G, Derwish A, Cataldi A, Schettino A, Occhionorelli
S, Donini I
Istituto di Clinica Chirurgica, Universita degli Studi, Ferrara.

HYPOTHESIS: To create a phlebolymphologic therapy in order: to activate
venous system; to activate lymphatic system; to activate macrophagic
system; to reduce the proteic lymphatic load. EXPERIMENTAL: A study was
performed on the use of an ideal phlebolymphological association (Tonka
Beans, Gingko Biloba, Melilotus Officinalis) as a practical standpoint in
the treatment of lymphedema of lower limbs in order to create an
efficacious dose of Coumarin, Benzopyrones and Ginkolidi. CLINICAL: We
investigated a population of 76 patients treated in an open-label study for
six-eight months with a dosage of Coumarin 60 mg/daily + Gingko Biloba 40
mg/daily + Melilotus 40 mg/daily. CONCLUSION: This trilogy induced a very
significant improvement in lymphedema (centimeter-aspect) both in
functional symptoms (pain heaviness in affected limbs) and physical signs
(edema, episodes of infection). Tolerance of long term treatment was good
and the improvement was observed from the third month of treatment.

===========================================================
24.)[Gingko biloba extract EGb 761 and pentoxifylline in intermittent
claudication. Secondary analysis of the clinical effectiveness].
===========================================================
Vasa 1992;21(4):403-10

Letzel H, Schoop W
Clinical trials on the efficacy of EGb 761 and pentoxifylline are
summarized in the context of their methods and results and compared with
each other. All placebo-controlled, randomized and double-blind studies
with the major target objective of "pain-free walking distance" were
selected. The pentoxifylline studies were adopted from a survey of the
existing literature in the English language, which has been brought up to
date via DIMDI research. The studies on both active substances are fraught
with similar difficulties as to method, and are not different as regards
their quality. The increase in walking distance is highly variable,
especially in the pentoxifylline studies. On average through each and all
of the studies on both preparations, an increase of 45% (EGb 761) or 57%
(pentoxifylline) in relation to initial values is here found. No
differences in the documentation of efficacy and the clinical efficacy were
discovered between the two substances, both of which are registered as
effective substances in the treatment of peripheral arterial occlusion
(pAO) in accordance with the Federal German Drugs Law (Arzneimittelgesetz,
AMG) of 1976.

===========================================================
25.)[Placebo-controlled double-blind study of the effectiveness of Ginkgo
biloba special extract EGb 761 in trained patients with intermittent
claudication]
===========================================================
Author
Blume J; Kieser M; H¨olscher U
Address
Angiologische Gemeinschaftspraxis, Aachen.
Source
Vasa, 25(3):265-74 1996
Abstract
This monocenter, randomized, placebo-controlled double-blind study
with parallel-group
comparison was carried out in order to demonstrate the efficacy of
Ginkgo biloba special
extract EGb 761 on objective and subjective parameters of the walking
performance in
trained patients suffering from peripheral arterial occlusive disease
in Fontaine stage IIb. In
total 60 patients were recruited (42 men; aged 47-82 years) with
angiographically proven
peripheral arterial occlusive disease of the lower extremities and an
intermittent claudication
existing for at least 6 months. No improvement had been shown despite
consistent walking
training and a maximum pain-free walking distance on the treadmill of
less than 150 m was
recorded at the beginning of the study. The therapeutic groups were
treated with either
Ginkgo biloba special extract EGb 761 at a dose of 3 times 1
film-coated tablet of 40 mg
per day by oral route or placebo over a duration of 24 weeks following
a two-week placebo
run-in phase. The main outcome measure was the difference of the
walking distance between
the start of treatment and after 8, 16 and 24 weeks of treatment as
measured on the treadmill
(walking speed 3 km/h and slope of 12%). As secondary parameters the
corresponding
differences for the maximum walking distance, the relative increase of
the pain-free walking
distance, the Doppler index and the subjective evaluation of the
patients were analyzed. The
absolute changes in the pain-free walking distance in treatment weeks
8, 16 and 24 as against
the treatment beginning (median values with 95% confidence interval)
led to the following
values for the patients treated with Ginkgo biloba special extract EGb
761:19 m (14, 33), 34
m (18, 50) and 41 m (26, 64). The corresponding values in the placebo
group were as
follows: 7 m (-4, 12), 12 m (5, 22) and 8 m (-1, 21). The advantage of
the EGb 761-treated
group as compared to the placebo group could be verified statistically
at the 3 time points
with p < 0.0001, p = 0.0003 and p < 0.0001. The test for the presence
of a clinically relevant
difference of 20% between EGb 761 and placebo also produced a
statistically significant
result (p = 0.008). The Doppler index remained unchanged in both
therapeutic groups: A
corresponding statistically significant advantage for the EGb 761
group was observed on a
descriptive level for the other parameters tested. The tolerance of
the treatment was very
good. The results of this placebo-controlled study show that treatment
with Ginkgo biloba
special extract EGb 761 produces a statistically highly significant
and clinically relevant
improvement of the walking performance in trained patients suffering
from intermittent
claudication with very good tolerance of the study preparation.

===========================================================
26.)[Ginkgo biloba in treatment of intermittent claudication. A systematic
research based on controlled studies in the literature]
===========================================================
Author
Ernst E
Address
Postgraduate Medical School, University of Exeter/UK.
Source
Fortschr Med, 114(8):85-7 1996 Mar 20
Abstract
The aim of this systematic review was to evaluate the effectiveness of
ginkgo biloba in the
treatment of intermittent claudication. A Medline-search identified
ten controlled trials on the
subject. These were heterogeneous in all respects and, with only few
exceptions, of poor
methodological quality. All the studies implied that ginkgo biloba is
an effective therapy for
intermittent claudication. This hypothesis should be confirmed in
further trials employing
meticulous methodology. Furthermore it would also be important to
determine whether oral
ginkgo biloba can be usefully combined with walking exercise.

===========================================================
27.)Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal
alterations.
===========================================================
Lens Eye Toxic Res 1992;9(3-4):521-8

Droy-Lefaix MT, Vennat JC, Besse G, Doly M
Laboratoire de Biophysique, Unite INSERM U71, Facultes de Medecine et de
Pharmacie, Clermont-Ferrand, France.

Electroretinography was used to investigate the preventive action of Ginkgo
biloba extract (EGb 761) in experimental chloroquine-induced retinopathy in
rats. EGb 761 contains flavones and anthocyanosides known for their
oxygenated radical scavenging properties. Chronic administration of
chloroquine (20 days) caused an overall lengthening of the duration of the
ERG b-wave, together with delayed peaking. These anomalies became more
marked with increased duration of treatment. In rats treated simultaneously
with chloroquine and EGb 761 no such modification of the electroretinogram
(ERG) was observed. These results suggest that retinal toxicity may be
related to a localized inflammation releasing oxygenated free radicals
and/or PAF. EGb 761 may thus afford a useful preventive treatment for
chloroquine-induced retinopathy, and generally for xenobiotic
retinotoxicities.

===========================================================
28.)Ginkgo biloba extract increases ocular blood flow velocity.
===========================================================
Author
Chung HS; Harris A; Kristinsson JK; Ciulla TA; Kagemann C; Ritch R
Address
Glaucoma Research and Diagnostic Center, Department of Ophthalmology,
Indiana University Medical Center, Indianapolis 46202, USA.
Source J Ocul Pharmacol Ther, 15(3):233-40 1999 Jun
Abstract
We evaluated a possible therapeutic effect of Ginkgo biloba extract
(GBE) on glaucoma patients that may benefit from improvements in ocular
blood flow. A
Phase I cross-over trial of GBE with placebo control in 11 healthy
volunteers (8 women,
3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were
treated with
either GBE 40 mg or placebo three
times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum
2000) was used to measure ocular blood flow before and after treatment.
There was a
two week washout period between GBE and placebo treatment. Ginkgo biloba
extract
significantly increased end diastolic velocity (EDV) in the ophthalmic
artery (OA)
(baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change,
p=0.023),
with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs
7.1 +/- 0.5
cm/sec, 3% change,
p=0.892). No side effects related to GBE were found. Ginkgo biloba extract
did not alter
arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract
significantly increased
EDV in the OA and deserves further investigation in ocular blood flow and
neuroprotection for possible application to the treatment of glaucomatous
optic
neuropathy as well as other ischemic ocular diseases.

===========================================================
29.)Pretreatment of skin with a Ginkgo biloba extract/sodium
carboxymethyl-beta-1,3-glucan formulation appears to inhibit the
elicitation of allergic contact dermatitis in man.
===========================================================
Author
Castelli D; Colin L; Camel E; Ries G
Address
RoC Laboratoires de Dermo-esth´etique, Colombes, France.
Source
Contact Dermatitis, 38(3):123-6 1998 Mar
Abstract
The clinical efficiency of mitigating contact dermatitis with a Ginkgo
biloba extract and carboxymethyl-beta-1,3-glucan formulation was
investigated in a double-blind versus placebo study using 22 subjects
(Caucasian women aged 22-55 years) with allergic contact dermatitis from
various substances in the European standard series. The formulation was
applied to intact skin 2X a day for 2 weeks ("in use" application) prior to
a single application of a selected contact allergen under a Finn Chamber
for 24 h. Readings were carried out in a blind study by a dermatologist 2
and 3 days after patch removal. Representative photographs were taken of
treated, placebo and untreated test areas. 68.2% of the panelists showed
significantly reduced skin reactivity (p = 0.037*) on the treated site 2
days after patch removal, versus untreated and/or placebo sites. This
finding indicates that the Ginkgo biloba/carboxymethyl-beta-1,3-glucan
formulation can mitigate against allergic contact dermatitis.
Language

===========================================================
30.)The effect of Gingko biloba extract (Egb 761) as a free radical scavenger
on the survival of skin flaps in rats. A comparative study.
===========================================================
Scand J Plast Reconstr Surg Hand Surg 1998 Jun;32(2):135-9

Bekerecioglu M, Tercan M, Ozyazgan I
Department of Plastic and Reconstructive Surgery, Faculty of Medicine,
Yuzuncu Yil University, Van, Turkey.

Free radicals may have a role in pedicle flap necrosis. We undertook this
study to compare the effect of various antioxidants and scavengers of free
radicals such as vitamin E, vitamin C, deferoxamine, and Gingko biloba
extract (Egb 761) on McFarlane caudal-based dorsal rat flaps. Fifty rats
were divided into five groups of 10 animals each. One group served as a
control (saline) group. The remaining four groups were given vitamin C 340
mg/kg, deferoxamine 150 mg/kg, Egb 761 100 mg/kg, and vitamin E 20 mg/kg.
The necrosed area of flap was significantly reduced in the deferoxamine (p
< 0.001), Egb 761 (p < 0.001), and vitamin C (p < 0.05) groups compared
with the control group. Vitamin E had no effect on distal flap necrosis (p
= 0.20).

===========================================================
31.)Induction of superoxide dismutase and catalase activity in different rat
tissues and protection from UVB irradiation after topical application of
Ginkgo biloba extracts.
===========================================================
Author
Lin SY; Chang HP
Address
Department of Medical Research and Education, Veterans General Hospital,
Taipei, Taiwan, Republic of China.
Source
Methods Find Exp Clin Pharmacol, 19(6):367-71 1997 Jul-Aug
Abstract
Ginkgo biloba extract (GBE) prepared from the leaves of Ginkgo biloba with
50% diluted alcohol was found to locally induce superoxide dismutase (SOD)
and catalase (CAT) enzyme activity in epidermis after topical application,
and also to systemically increase the activity of both enzymes in the
liver, heart and kidney of Sprague Dawley rats. Skin pretreated with 50%
diluted alcohol-extracted liquid formulation was protected from
exacerbation of UVB damage. Changes in the lipid structure of the skin of
rats determined by ATR/FT-IR spectroscopy demonstrated penetration of
active components from GBE dosage formulations.


===========================================================
32.)In vivo regulation of peripheral-type benzodiazepine receptor and
glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated
ginkgolides.
===========================================================
Author
Amri H; Ogwuegbu SO; Boujrad N; Drieu K; Papadopoulos V
Address
Department of Cell Biology, Georgetown University Medical Center,
Washington, District of Columbia 20007, USA.
Source
Endocrinology, 137(12):5707-18 1996 Dec
Abstract
Glucocorticoid excess has broad pathogenic potential including
neurotoxicity, neuroendangerment, and immunosuppression. Glucocorticoid
synthesis is regulated by ACTH, which acts by accelerating the transport of
the precursor cholesterol to the mitochondria where steroidogenesis begins.
Ginkgo biloba is one of the most ancient trees, and extracts from its
leaves have been used in traditional medicine. A standardized extract of
Ginkgo biloba leaves, termed EGb 761 (EGb), has been shown to have
neuroprotective and antistress effects. In vivo treatment of rats with EGb,
and its bioactive components ginkgolide A and B, specifically reduces the
ligand binding capacity, protein, and messenger RNA expression of the
adrenocortical mitochondrial peripheral-type benzodiazepine receptor (PBR),
a key element in the regulation of cholesterol transport, resulting in
decreased corticosteroid synthesis. As expected, the ginkgolide-induced
decrease in glucocorticoid levels resulted in increased ACTH release, which
in turn induced the expression of the steroidogenic acute regulatory
protein. Because ginkgolides reduced the adrenal PBR expression and
corticosterone synthesis despite the presence of high levels of
steroidogenic acute regulatory protein, these data demonstrate that PBR is
indispensable for normal adrenal function. In addition, these results
suggest that manipulation of PBR expression could control circulating
glucocorticoid levels, and that the antistress and neuroprotective effects
of EGb are caused by to its effect on glucocorticoid biosynthesis.

===========================================================
33.)Reactive oxygen metabolites, antioxidants and head and neck cancer.
Author
===========================================================
Seidman MD; Quirk WS; Shirwany NA
Address
Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital,
6777 W. Maple Road, W. Bloomfield, MI 48323, USA.
Source
Head Neck, 21(5):467-79 1999 Aug
Abstract
This manuscript will review the probable role of reactive oxygen
metabolites (ROM) in the etiopathogenesis of head and neck cancer (HNC).
Cancer is a heterogeneous disorder with multiple etiologies including
somatic and germ-line mutations, cellular homeostatic disturbances, and
environmental triggers. Certain etiologies are characteristic of HNC and
include infectious agents such as the Epstein-Barr virus, the use of
tobacco, and consumption of alcohol. A large body of evidence implicates
ROM in tumor formation and promotion. ROM species are formed in the process
of cellular respiration, specifically during oxidative phosphorylation.
These ubiquitous molecules are highly toxic in the cellular environment. Of
the many effects of ROM, especially important are their effect on DNA.
Specifically, ROM cause a variety of DNA damage, including insertions,
point mutations, and deletions. Thus, it is hypothesized that ROM may be
critically involved in the etiology of malignant disease through their
possible impact on protooncogenes and tumor suppressor genes. Additionally,
empirical evidence suggests that ROM may also affect the balance between
apoptosis and cellular proliferation. If apoptotic mechanisms are
overwhelmed, uncontrolled cellular proliferation may follow, potentially
leading to tumor formation. Thus, this manuscript will critically review
the evidence that supports the role of ROM in tumorigenesis. ROM scavengers
and blockers have shown both in vivo and in vitro effects of attenuating
the toxicity of ROM. Such compounds include the antioxidant vitamins (A, C,
and E), nutrient trace elements (selenium), enzymes (superoxide dismutase,
glutathione peroxidase, and catalase), hormones (melatonin), and a host of
natural and synthetic compounds (lazaroids, allopurinol, gingko extract).
Thus, this paper will also review the possible benefit derived from the use
of such scavengers/blockers in the prevention of HNC. Copyright 1999 John
Wiley & Sons, Inc. Head Neck 21: 467-479, 1999.

===========================================================
34.)Protective effects of Gingko biloba extract EGb 761 on myocardium of
experimentally diabetic rats. I: ultrastructural and biochemical
investigation on cardiomyocytes.
===========================================================
Exp Toxicol Pathol 1999 May;51(3):189-98

Fitzl G, Martin R, Dettmer D, Hermsdorf V, Drews H, Welt K
Institute of Anatomy, University Leipzig, Germany.

Chronic diabetes in man and animal models develops cardiomyopathic
alterations which cannot be absolutely avoided by insuline therapy. Since
diabetic damage is partly attributed to oxidative stress antioxidative
treatment could be able to reduce the alterations. Aim of this study was to
investigate the cardioprotective effects of EGb 761, known as a radical
scavenger, against diabetic alterations in rats. The diabetes was induced
by i.p. injection of 60 mg/kg body weight streptozotocin. Duration of
diabetes was 4 months, the protected group received 100 mg/kg body weight
EGb 761 with the drinking water over 3 months. Electron and light
microscopic morphometry of left-ventricular samples revealed typical
diabetic alterations consisting in decrease of volume fraction of
myofibrils, SR and t-tubules and diminishing of cardiomyocyte diameter,
increase of interstitial volume, mitochondrial size and volume fraction,
and of vacuoles and of lipid drops. EGb treatment could gradually prevent
the loss of myofibrils and reduction of myocyte diameter but has only
little influence on interstitial and mitochondria volume. The
diabetic-induced increase of lipid and vacuoles and the decrease of SR and
t-tubules were not influenced. Biochemical parameters of oxidative stress:
malondialdehyde (MDA) was only insignificantly altered by diabetes and EGb.
The superoxide dismutase (SOD) activity was increased by diabetes and more
increased by EGb treatment. Creatine kinase (CK) activity was diminished by
diabetes but slightly increased by EGb. The polymerase chain reaction (PCR)
of i-NOS was not different between the diabetic and protected diabetic
groups.

===========================================================
45.)Identification of Gingko biloba flavonol metabolites after oral
administration to humans.
===========================================================
J Chromatogr B Biomed Sci Appl 1997 May 23;693(1):249-55

Pietta PG, Gardana C, Mauri PL
CNR-ITBA, Milan, Italy.

An extract of Ginkgo biloba leaves (EGb) was given to healthy volunteers.
Urine samples were collected for 3 days, and blood samples were withdrawn
every 30 min for 5 h. The samples were purified through SPE C18 cartridges
and analyzed by reversed-phase LC-diode array detection for the presence of
EGb metabolites. Only urine samples contained detectable amounts of
substituted benzoic acids, i.e., 4-hydroxybenzoic acid conjugate,
4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid,
3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid and
3-methoxy-4-hydroxybenzoic acid (vanillic acid). In contrast to rats no
phenylacetic acid or phenylpropionic acid derivatives were found in urine,
thus indicating that in humans a more extensive metabolism takes place. As
for rats the metabolites found in human urines accounted for less than 30%
of the flavonoids given. The same procedure was applied to blood samples,
and no metabolites could be detected.

===========================================================
46.)Solid-phase extraction and gas chromatography-mass spectrometry
determination of kaempferol and quercetin in human urine after consumption
of Ginkgo biloba tablets.
===========================================================
Author
Watson DG; Oliveira EJ
Address
Department of Pharmaceutical Sciences, University of Strathclyde,
Strathclyde Institute of Biomedical Sciences, Glasgow, UK.
d.g.watson@strath.ac.uk
Source
J Chromatogr B Biomed Sci Appl, 723(1-2):203-10 1999 Feb 19
Abstract
A method was developed for the quantification of the flavonoids quercetin
and kaempferol in human urine using a solid-phase extraction procedure
followed by gas chromatography-mass spectrometry. Deuterated internal
standards of the analytes were spiked into the samples prior to extraction.
The limit of detection of the method was ca. 10 pg on column and precision
of the method for quantification in a sample of urine was +/-9.40% for
kaempferol and +/-7.34% for quercetin (n = 6). The levels of quercetin and
kaempferol found in urine samples were only a small fraction of the amount
ingested. The treatment of urine samples with beta-glucuronidase markedly
increased the levels of flavonoids detected, supporting the view that
kaempferol and quercetin are eliminated in the urine as glucuronides.
Language

===========================================================
47.)Ginkgo biloba extract (EGb 761) independently improves changes in passive
avoidance learning and brain membrane fluidity in the aging mouse.
===========================================================
Pharmacopsychiatry 1996 Jul;29(4):144-9

Stoll S, Scheuer K, Pohl O, Muller WE
Central Institute for Mental Health, Section Psychopharmacology, Mannheim,
Germany.

Decreases in cell membrane fluidity may be a major mechanism of age-related
functional decline. A prime cause for the decline of membrane fluidity may
be the presence of free radicals. Gingko biloba extract EGb 761 protects
neuronal cell membranes from free radical damage in vitro. Further, EGb 761
has repeatedly been shown to improve cognitive functions in man and in
laboratory animals. To test if there is a link between these two actions we
assessed the effects of EGb 761 on passive avoidance learning and on
neuronal membrane fluidity in vivo in young (three-month-old), middle-aged
(12-month-old) and aged (22 to 24-month-old) female NMRI mice. The animals
were treated daily with 100 mg/kg EGb 761 for three weeks. There was a
significant improvement in short-term memory, measured by the avoidance
latency 60 seconds after the aversive stimulus (p < 0.0311), and of
membrane fluidity (p < 0.01) in the aged animals, but no improvement in
long-term memory as measured by the avoidance latency 24 hours after shock.
However, no significant correlation between membrane fluidity and
short-term memory performance was found. Taken together, these results
indicate that EGb 761 independently improves changes in passive avoidance
learning and brain membrane fluidity.

===========================================================
48.)Lipid peroxidation in experimental spinal cord injury. Comparison of
treatment with Ginkgo biloba, TRH and methylprednisolone.
===========================================================
Res Exp Med (Berl) 1995;195(2):117-23

Koc RK, Akdemir H, Kurtsoy A, Pasaoglu H, Kavuncu I, Pasaoglu A, Karakucuk I
Department of Neurosurgery, Erciyes University, School of Medicine,
Kayseri, Turkey.

Ischaemia-induced lipid peroxidation is one of the most important factors
producing tissue damage in spinal cord injury. In our study, the protective
effects of Ginkgo biloba, thyroid releasing hormone (TRH) and
methylprednisolone (MP) on compression injury of the rat spinal cord were
investigated. For this study 45 rats in four groups, including control, MP,
TRH and Gingko biloba, were used to determine the formation of
malondialdehyde (MDA). All the animals were made paraplegic by the
application clip method of Rivlin and Tator. Rats were divided randomly and
blindly to one of four treatment groups (ten animals in each). MP and
Ginkgo biloba treatments significantly decreased MDA levels (F = 54.138, P
< 0.01). These results suggest that MP and Ginkgo biloba may have a
protective effect against ischaemic spinal cord injury by the antioxidant
effect.

===========================================================
49.)A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by
protecting against oxidative stress.
===========================================================
Author
Sastre J; Mill´an A; Garc´ia de la Asunci´on J; Pl´a R; Juan G; Pallard´o;
O'Connor E; Martin JA; Droy-Lefaix MT; Vi~na J
Address
Departamento de Fisiolog´ia, Facultad de Medicina, Univ. Valencia, Spain.
Source
Free Radic Biol Med, 24(2):298-304 1998 Jan 15
Abstract
The effect of aging on indices of oxidative damage in rat mitochondria and
the protective effect of the Ginkgo biloba extract EGb 761 was
investigated. Mitochondrial DNA from brain and liver of old rats exhibited
oxidative damage that is significantly higher than that from young rats.
Mitochondrial glutathione is also more oxidized in old than in young rats.
Peroxide formation in mitochondria from old animals was higher than in
those from young ones. According to morphological parameters (size and
complexity), there are two populations of mitochondria. One is composed of
large, highly complex mitochondria, and the other population is smaller and
less complex. Brain and liver from old animals had a higher proportion of
the large, highly complex mitochondria than seen in organs from young
animals. Treatment with the Ginkgo biloba extract EGb 761 partially
prevented these morphological changes as well as the indices of oxidative
damage observed in brain and liver mitochondria from old animals.

===========================================================
50.)The correlation of cytophotometrically and biochemically measured enzyme
activities: changes in the myocardium of diabetic and hypoxic diabetic
rats, with and without Ginkgo biloba extract treatment.
===========================================================
Author
Punkt K; Adams V; Linke A; Welt K
Address
Institute of Anatomy, University of Leipzig, Germany.
Source
Acta Histochem, 99(3):291-9 1997 Aug
Abstract
Changes of enzyme activities in the myocardium of rats from 6 different
experimental groups (normal rats, diabetic rats, hypoxic diabetic rats,
each with and without Ginkgo biloba extract treatment) were measured by
using both cytophotometric and biochemical methods. The activity of
succinate dehydrogenase, a marker of oxidative capacity, and of
menadione-dependent glycerol-3-phosphate dehydrogenase and total lactate
dehydrogenase, both markers of glycolytic capacity were measured to
characterize changes of the metabolic profile in myocardium. A strong
correlation between cytophotometric and biochemical data were found by
linear regression analysis, justifying the use of cytophotometrical enzyme
activity measurements in cells of organized tissue, where biochemistry
cannot provide topographical information. The comparison of the results
obtained from the different groups revealed the following: Enzyme
activities in the myocardium of rats with streptozotocin-induced diabetes
were significantly increased by 10-30% as compared to the normal
myocardium. This effect was interpreted as a metabolic compensation of the
diabetic heart with reduced performance. When diabetic rats were exposed to
acute hypoxia of 20 min duration, enzyme activities decreased under the
normal level, to 56% of the succinate dehydrogenase activity, to 87% of
glycerol-3-phosphate dehydrogenase activity and to 69% of lactate
dehydrogenase activity. Treatment of rats with the oxygen radical scavenger
Ginkgo biloba extract (EGb 761) over 3 months resulted primarily in an
increase by 10% of oxidative capacity and in a decrease by 30% of
glycolytic capacity. Under diabetic conditions a shift to more glycolytic
metabolism was observed by increasing the glycolytic activity by 39% and
remaining the oxidative activity.

===========================================================
51.)Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse
fibrosarcoma.
===========================================================
Author
Ha SW; Yi CJ; Cho CK; Cho MJ; Shin KH; Park CI
Address
Laboratory of Radiation Biology, Seoul National University Medical College,
South Korea.
Source
Radiother Oncol, 41(2):163-7 1996 Nov
Abstract
BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to
increase peripheral blood circulation. The hypothesis that GBE may be able
to enhance radiosensitivity of tumor by improving tumor blood flow and thus
decreasing hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma
(FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was
given i.p. 1 h before irradiation with or without priming dose given 1 day
earlier. Effect on tumor and normal tissue radiation reaction was
investigated. RESULTS: Tumor growth delay by radiation was more elongated
after two doses (1-day interval) of GBE than after a single dose. Radiation
dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy
to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06
(1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2%
(3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two
doses (P < 0.001). Radiation effect on normal tissue, estimated by acute
skin reaction and jejunal crypt assay, was not affected by GBE. CONCLUSION:
Ginkgo biloba extract enhances radiation effect on tumor without increasing
acute normal tissue radiation damage in this model system probably by
increasing tumor blood flow and further investigation for this possible
radiosensitizer is needed.

===========================================================
52.)Platelet-activating factor is an important mediator in hypoxic ischemic
brain injury in the newborn rat. Flunarizine and Ginkgo biloba extract
reduce PAF concentration in the brain.
===========================================================
Author
Akis¨u M; K¨ult¨ursay N; Coker I; H¨useyinov A
Address
Department of Pediatrics, Ege University Medical School, Izmir, Turkey.
makisu@med.ege.edu.tr
Source
Biol Neonate, 74(6):439-44 1998 Dec
Abstract
Hypoxic-ischemic encephalopathy is still a very important cause of neonatal
mortality and morbidity. Recently, platelet-activating factor (PAF) has
been accused of being responsible for the neuronal damage in
hypoxic-ischemic brain. We investigated tissue PAF concentrations in
hypoxic-ischemic brain injury in immature rats. Endogenous PAF
concentration in brain tissue showed a marked increase in hypoxic-ischemic
pups (85.6 +/- 15.5 pg/mg protein) when compared to that of control (9.05
+/- 3.1 pg/mg protein). In addition, we examined the effects of
flunarizine, a selective calcium channel blocker, and Ginkgo biloba extract
(EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain injury.
Endogenous PAF concentrations in both flunarizine-pretreated (16.6 +/- 4.8
pg/mg protein) and EGb 761-pretreated (33.5 +/- 8.9 pg/mg protein) pups
were significantly lower than the untreated group. These results indicate
that PAF is an important mediator in immature rat model of cerebral
hypoxic-ischemic injury. The suppressor effect of flunarizine and EGb 761
on PAF production may open new insight into the treatment of
hypoxic-ischemic brain injury.

===========================================================
53.)The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid
peroxide, some free radical scavengers and the cardiovascular system of
aged rats.
===========================================================
Author
al-Zuhair H; Abd el-Fattah A; el-Sayed MI
Address
Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh,
Saudi Arabia.
Source
Pharmacol Res, 38(1):65-72 1998 Jul
Abstract
Aged rats are highly prone to many physiological changes such as blood
pressure and heart rate. These changes could be due to modification in
membrane phospholipid composition of their blood vessels. Lipid peroxide in
vivo has been identified as a basic deteriorative reaction in cellular
mechanisms of aging in human. The effect of a nootropic drug, meclofenoxate
(MF) or its combination with extract of ginkgo biloba (EGb-761) or zinc
(Zn) on malondialdehyde (MDA) product as an index of endogenous lipid
peroxidation; phospholipid; glutathione (GSH) and protein thiols (PrSHs)
contents as well as superoxide dismutase (SOD) activity in blood, brain,
heart and liver of 24-month-old male rats was investigated. Aged rats were
treated with MF once daily at oral doses of 100 mg kg-1 body wt. alone or
with either EGb at a dose of 150 mg kg-1 body wt. or Zn at 10.5 mg kg-1
body wt. for 4 weeks. This study showed that aging caused a higher
increment in MDA level of brain and heart than liver and plasma accompanied
with reduction in brain and heart phospholipid contents as well as
alteration of the antioxidant systems as compared to 4-month-old rats.
Treatment of aged rats with MF alone or combined with either EGb or Zn
caused improvement in the measured free radical scavengers especially in
brain and heart tissues. Our results also showed that both EGb and Zn
induced a significant potential effect of MF action on blood pressure and
heart rate. The results were explained in the light of the antioxidant
properties of EGb and Zn. Thus it is concluded that EGb and Zn have a
beneficial role with MF in diminishing cumulative oxidative changes in aging.

===========================================================
54.)Effects on skeletal muscle fibres of diabetes and Ginkgo biloba
extract treatment.
===========================================================
Author
Punkt K; Psinia I; Welt K; Barth W; Asmussen G
Address
Institute of Anatomy, University of Leipzig, Germany.
Source
Acta Histochem, 101(1):53-69 1999 Feb
Abstract
Combined cytophotometric and morphometric analysis of muscle fibre
properties and myosin
heavy chain electrophoresis were performed on extensor digitorum
longus and soleus muscles
from healthy rats and rats with streptozotocin-induced diabetes.
Moreover, the protective
effect of Ginkgo biloba extract, a potent oxygen radical scavenger, on
diabetic muscles was
investigated. Changes in fibre type-related enzyme activities, fibre
type distribution, fibre cross
areas and myosin isoforms were found. In muscles of diabetic rats, a
metabolic shift was
measured mainly in fibres with oxidative metabolism. Fast-oxidative
glycolytic fibres showed a
shift to more glycolytic metabolism and about a third transformed into
fast-glycolytic fibres.
Slow-oxidative fibres became more oxidative. Fibre atrophy was
measured in diabetic
muscles dependent on fibre type and muscle. Different fibre types
atrophied to a different
degree. Therefore, a decreased area percentage of slow fibres and an
increased area
percentage of fast fibres of the whole muscle cross section in both
muscles were found. This is
supported by reduced slow and increased fast myosin heavy chain
isoforms. These alterations
of diabetic muscle fibres could be due to less motion of diabetic rats
and diabetic neuropathy.
After treatment with Ginkgo biloba extract, enzyme activities were
increased mainly in
oxidative fibres of diabetic muscles, which was interpreted as
protective effect. Generally, the
soleus muscle with predominant oxidative metabolism was more
vulnerable to diabetic
alterations and Ginkgo biloba extract treatment than the extensor
digitorum longus muscle
with predominant glycolytic metabolism.

===========================================================
55.)The effects of prostaglandin E2 indomethacin & Ginkgo biloba extract
on resistance to experimental sepsis.
===========================================================
Author
Cant¨urk NZ; Utkan NZ; Cant¨urk Z; Yenisey C; Yildirir C; D¨ulger M
Address
Kocaeli University, Faculty of Medicine, Department of Surgery,
Kocaeli, Turkey.
Source
Indian J Med Res, 108():88-92 1998 Sep
Abstract
We investigated the effect of 16,16-dimethyl prostaglandin E2
indomethacin and Ginkgo
biloba extract on the survival in two experimental sepsis models in
rats due to administration
of 1 x 10(7) cfu and 1 x 10(9) cfu Escherichia coli. Animals in each
model were then
randomly divided (10/group) into four groups, administered saline,
indomethacin, G. biloba
extract and prostaglandin E2 respectively. When compared, there was no
significant
difference in the survival period between the two sepsis models (P >
0.05). The best survival
rate was observed in the PGE2-administered animals in the first major
model (P < 0.05).
Indomethacin appeared not to decrease the mortality rates. There was
no significant
difference in PGE2 levels between two sepsis models (P > 0.05). Our
results suggest that
elevated prostaglandin E2 levels following major trauma are not
responsible for the postinjury
increased susceptibility to infectious complications. Our observations
should also discourage
aggressive use of cyclo-oxygenase inhibitors for protection against
infectious complications
after major trauma.

===========================================================
56.)Ginkgo biloba extract protects brain neurons against oxidative stress
induced by hydrogen peroxide.
===========================================================
Author
Oyama Y; Chikahisa L; Ueha T; Kanemaru K; Noda K
Address
Laboratory of Cell Signaling (Pharmacology), Faculty of Integrated
Arts and Sciences,
University of Tokushima, Japan.
Source
Brain Res, 712(2):349-52 1996 Mar 18
Abstract
Effect of Ginkgo biloba extract was examined on dissociated rat
cerebellar neurons suffering
from oxidative stress induced by hydrogen peroxide using a flow
cytometer and ethidium
bromide. Hydrogen peroxide at a concentration of 3 mM increased the
number of neurons
stained with ethidium (presumably dead neurons) in a time-dependent
manner. Pretreatment
of neurons with G. biloba extract (10 micrograms/ml) greatly delayed a
time-dependent
increase in number of dead neurons during exposure to hydrogen
peroxide. It was true, but
less effective, in the case of treatment with G. biloba extract
immediately or 60 min after start
of oxidative stress. Results implicate G. biloba extract as a
potential agent in protecting the
neurons suffering from oxidative stress induced by hydrogen peroxide.


========================================================
63.) Alternative Systemic Treatments for Vitiligo: A Review.
=======================================================
Am J Clin Dermatol. 2015 Dec;16(6):463-74. doi: 10.1007/s40257-015-0153-5.

Cohen BE1, Elbuluk N1, Mu EW1, Orlow SJ2.
Author information

1
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 240 East 38th Street, New York, NY, 10016, USA.
2
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 240 East 38th Street, New York, NY, 10016, USA. seth.orlow@nyumc.org.

Abstract

Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on L-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.
===================================================
64.) Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial.
==================================================
BMC Complement Altern Med. 2011 Mar 15;11:21. doi: 10.1186/1472-6882-11-21.

Szczurko O1, Shear N, Taddio A, Boon H.
Author information

1
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, 130 Dundas St East, Suite 305, Mississauga, ON L5A 3V8, Canada. orest@noumena.ca

Abstract
BACKGROUND:

Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.
METHODS:

12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized G. biloba two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.
RESULTS:

After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.
CONCLUSIONS:

The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.
===================================================
65.) Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system.
===================================================
Phytomedicine. 2016 Nov 15;23(12):1356-1364. doi: 10.1016/j.phymed.2016.07.013. Epub 2016 Aug 1.

Kim MS1, Bang JH2, Lee J1, Han JS3, Baik TG4, Jeon WK5.
Author information

1
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea.
2
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea.
3
Department of Biological Science, Konkuk University, Seoul 05029, The Republic of Korea.
4
Central Research Center, Yuyu Pharma. Inc., Seoul 04598, The Republic of Korea.
5
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea. Electronic address: wkjeon@kiom.re.kr.

Abstract
BACKGROUND:

Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH).
PURPOSE:

In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo).
METHODS:

Chronic BCCAo was induced in adult male Wistar rats to reflect the CCH conditions. On day 21 after BCCAo, the animals were treated orally with saline or GBE (5, 10, 20, and 40mg/kg) daily for 42 days. After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs).
RESULTS:

BCCAo increased glial proliferation in the hippocampus and white matter, whereas proliferation was significantly attenuated by GBE treatment. GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). Furthermore, GBE treatment restored the ChAT expression in the basal forebrain following BCCAo.
CONCLUSIONS:

These findings suggest that GBE has specific neuroprotective effects that may be useful for the treatment of CCH. The pharmacological mechanism of GBE partly involves the modulation of inflammatory mediators and the cholinergic system.
===================================================
66.) Effect of Ginkgo biloba Extract (EGb-761) on Recovery of Erectile Dysfunction in Bilateral Cavernous Nerve Injury Rat Model.
===================================================
Urology. 2015 May;85(5):1214.e7-15. doi: 10.1016/j.urology.2015.01.026. Epub 2015 Mar 13.

Wu YN1, Liao CH2, Chen KC3, Liu SP4, Chiang HS5.
Author information

1
Ph.D. Program in Nutrition and Food Sciences, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan; Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
2
Ph.D. Program in Nutrition and Food Sciences, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan; Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Surgery, Division of Urology, Cardinal Tien Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
3
Ph.D. Program in Nutrition and Food Sciences, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan; Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Urology, Cathay General Hospital, Taipei, Taiwan.
4
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
5
Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Surgery, Division of Urology, Cardinal Tien Hospital, New Taipei City, Taiwan; Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: 053824@mail.fju.edu.tw.

Abstract
OBJECTIVE:

To investigate whether the therapeutic effect of Ginkgo biloba extract (GBE) in a rat model can improve erectile dysfunction after bilateral cavernous nerve injury.
METHODS:

Forty-three male Sprague-Dawley rats underwent cavernous nerve crush injury and were randomized into 4 groups, including: vehicle only, high-dose GBE, medium-dose GBE, and low-dose GBE. Eight animals underwent sham operation. Four weeks later, erectile function was assessed by cavernous nerve electrostimulation, and penile tissue was collected for histologic analysis.
RESULTS:

Significant recovery of erectile function was observed in the high-dose GBE group in a dose-dependent manner as compared with the vehicle-only group (P <.001). The high-dose GBE group had a significant increase in neurofilament-1 expression (P <.001), preservation of neural nitric oxide synthase nerve fibers of the dorsal penile nerve (P <.05), and increased smooth muscle cell content (P <.001) compared with the vehicle-only group. In addition, high-dose GBE markedly augments the smooth muscle-to-collagen ratio (P <.05) and reduces the apoptotic index.
CONCLUSION:

Administration of GBE increases neuron survival and preserves the neural nitric oxide synthase nerve fiber and contents of the corpus cavernosum after bilateral cavernous nerve injury. These implications indicate the beneficial effects of GBE use in the repair of the cavernous nerve and recovery of erectile function after radical prostatectomy.

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67.) A Urologist's Guide to Ingredients Found in Top-Selling Nutraceuticals for Men's Sexual Health.
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J Sex Med. 2015 Nov;12(11):2105-17. doi: 10.1111/jsm.13013. Epub 2015 Nov 3.
Cui T1, Kovell RC1, Brooks DC1, Terlecki RP1.
Author information
1
Department of Urology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Abstract
INTRODUCTION:
Use of supplements is common among men seeking urologic evaluation for sexual health matters. With a dizzying array of formulations available and little regulation on the dosage, purity, or ingredients found in these products, the health effects of nutraceuticals are often confusing to patients and medical practitioners alike.
AIM:
In this review, we set out to concisely summarize the data on ingredients found within the top-selling nutraceutical agents marketed for men's sexual health in order to provide a clinical guide for urologists.
METHODS:
We used sales data from the most popular retail provider of men's health supplements to identify the top-selling products marketed toward improvement of men's sexual health. We summarized the available information related to the ingredients, dosage, cost, and mechanism of action for these substances and performed an extensive literature search to identify and review the current evidence available for each of the most common ingredients found in these nutraceuticals.
RESULTS:
The top-selling nutraceuticals marked for men's sexual health contain a blend of multiple supplements (up to 33 in one formulation identified), the most common being ginseng, tribulus, zinc, horny goat weed, B complex vitamins/trace minerals, fenugreek, L-arginine, maca, DHEA, ginkgo, and yohimbine. The currently available medical literature evaluating the efficacy of these substances is generally of low quality.
CONCLUSIONS:
Despite the dearth of evidence supporting nutraceutical agents in the men's health arena, these substances are still commonly used by patients. As these products can affect the health and well-being of men presenting to a urology clinic, a familiarity with commonly used agents can help the urologist appropriately counsel their patients.
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68.) Triple-blind, placebo-controlled trial of Ginkgo biloba in sexual dysfunction due to antidepressant drugs.
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Wheatley D1.
Author information
1
15 Elizabeth Court, Lower Kings Road, Kingston-on-Thames KT2 5HP, UK. wheatley@ukgateway.net
Abstract
A triple-blind (investigator, patient, statistician), randomized, placebo-controlled, trial of Ginkgo biloba 240 mg daily was carried out. Following a 1-week control, it was given to 24 patients with sexual impairment due to antidepressant drugs. Efficacy analysis was carried out on eight males and five females on placebo and six males and five females on Ginkgo, completing the full 12 weeks of treatment. Not included were three subjects who dropped out after 6 weeks. A validated, sex (gender)-orientated questionnaire was recorded at - 1, 0, 1, 3, 6, 9 and 12 weeks, and a non-blind follow-up for a further 6-weeks on Ginkgo. Hamilton anxiety and depression ratings were made at 0, 6 and 12 weeks and simple global assessments of alertness and memory. There were some spectacular individual responses in both groups, but no statistically significant differences, and no differences in side-effects.
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69.) Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 Jun;36(6):674-7.
[Treatment of Early Diabetic Retinopathy by Liuwei Dihuang Pill Combined Ginkao Leaf Tablet].
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[Article in Chinese]
An XF, Zhao Y, Yu JY.
Abstract
OBJECTIVE:
To observe the prevention and clinical efficacy of combination of Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic retinopathy (DR).
METHODS:
Using randomized, double-blind, double simulation, parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM) outpatients were recruited and assigned to the treatment group and the control group, 70 in each group. All patients received basic Western medicine treatment (such as blood glucose and pressure control). Patients in the treatment group took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times per day), while those in the control group took LDP placebos and GLT placebos. All treatment lasted for 24 consecutive months. All subjects were followed-up every month. The general clinical data as sex, age, and metabolic data such as blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected and statistically analyzed.
RESULTS:
There was no significant difference in levels of blood glucose, blood pressure, or blood lipid between the two groups (P > 0.05). After treatment the DR incidence rate was significantly lower in the treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P < 0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59), P < 0.05].
CONCLUSION:
Combination of LDP and GLT could effectively prevent and treat the development of DR in T2DM patients.
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70.) Neuroprotection in Glaucoma.
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Doozandeh A1, Yazdani S2.
Author information
1
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC) loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP) reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine) with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off-label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice.
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71.) Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports.
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J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2017 Jan 2;35(1):1-28. doi: 10.1080/10590501.2016.1278298.
Mei N1, Guo X1, Ren Z2, Kobayashi D3, Wada K3, Guo L2.
Author information
1
a Division of Genetic and Molecular Toxicology , National Center for Toxicological Research , Jefferson , Arkansas , USA.
2
b Division of Biochemical Toxicology , National Center for Toxicological Research , Jefferson , Arkansas , USA.
3
c Department of Food and Chemical Toxicology , Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido , Hokkaido , Japan.
Abstract
Ginkgo biloba seeds and leaves have been used as a traditional herbal remedy for thousands of years, and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents. The National Toxicology Program conducted 2-year gavage studies on one Ginkgo biloba leaf extract and concluded that there was clear evidence of carcinogenic activity of this extract in mice based on an increased incidence of hepatocellular carcinoma and hepatoblastoma. Recently, Ginkgo biloba leaf extract has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer. This review presents updated information on the toxicological effects from experimental studies both in vitro and in vivo to human case reports (caused by ginkgo seeds or leaves), and also summarizes the negative results from relatively large clinical trials.
 

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