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WHO Monographs on Selected Medicinal Plants - Volume 1
(1999; 295 pages) View the PDF document
Table of Contents
View the documentAcknowledgements
View the documentIntroduction
View the documentBulbus Allii Cepae
View the documentBulbus Allii Sativi
View the documentAloe
View the documentAloe Vera Gel
View the documentRadix Astragali
View the documentFructus Bruceae
View the documentRadix Bupleuri
View the documentHerba Centellae
View the documentFlos Chamomillae
View the documentCortex Cinnamomi
View the documentRhizoma Coptidis
View the documentRhizoma Curcumae Longae
View the documentRadix Echinaceae
View the documentHerba Echinaceae Purpureae
View the documentHerba Ephedrae
View the documentFolium Ginkgo
View the documentRadix Ginseng
View the documentRadix Glycyrrhizae
View the documentRadix Paeoniae
View the documentSemen Plantaginis
View the documentRadix Platycodi
View the documentRadix Rauwolfiae
View the documentRhizoma Rhei
View the documentFolium Sennae
View the documentFructus Sennae
View the documentHerba Thymi
View the documentRadix Valerianae
View the documentRhizoma Zingiberis
View the documentAnnex. Participants in the WHO Consultation on Selected Medicinal Plants
 

Folium Ginkgo

Definition

Folium Ginkgo consists of the dried whole leaf of Ginkgo biloba L. (Ginkgoaceae).

Synonyms

Pterophyllus salisburiensis Nelson, Salisburia adiantifolia Smith, Salisburia macrophylla C. Koch (1–4).

Selected vernacular names

Eun-haeng, gin-nan, ginkgo, ginkgo balm, ginkgo leaves, ginkyo, ginan, icho, ityo, kew tree, maidenhair tree, pei-wen, temple balm, yin guo, yinhsing (1–5).

Description

A monotypic dioecious plant that is the only living representative of the Ginkgoales. It has a grey bark, reaches a height of 35 m and a diameter of 3–4m (sometimes up to 7m), and has fan-like leaves that are deciduous, alternate, lengthily petiolate, bilobate, base wedge-shaped, 6–9cm broad (sometimes up to 15–20 cm), turning yellow in autumn. Venation dichotomously branching, seemingly parallel. Staminate and ovulate strobili borne on separate trees; staminate strobili consisting of naked pairs of anthers in catkin-like clusters; ovulate strobili in the form of long, slender, fused stalks bearing a single naked ovule which is fertilized by motile sperm cells, developing into 2 seeds. Seeds yellow when mature, foul-smelling, drupe-like, the middle layer of integument becoming hard or stone-like, the outer layer fleshy (3, 4).

Plant material of interest: dried leaf

The kernel (nut, seed) is used in Chinese medicine (6, 7).

General appearance

The leaves are green, grey-yellow, brown or blackish; the upper side of a leaf may be somewhat darker than the underside. The leaves are fan-shaped, longpetioled and have two lobes with forked veins radiating from the petiole end (2, 4, 8).

Organoleptic properties

Ginkgo leaves have a weak characteristic odour (2, 4, 8).

Microscopic characteristics

Young leaves have abundant trichomes that become confined to the petiole base as the leaf ages. While the leaves have no midrib, dichotomous venation with regular, numerous branching parallel veins arises from two vascular strands within the petiole. Stomata occur almost exclusively on the lower surface of the leaf. The epidermis of the upper and underside of the leaf consists of undulated, irregular, mostly long extended cells. In the cross-section, the epidermal cells appear nearly isodiametric and from above appear to be slightly undulated, with the upper cells appearing larger. The outer walls of the epidermal cells are covered with a more or less thin layer of cuticle. In the area of vascular bundles there are remarkable long extended narrow cells with slightly undulated walls. Numerous druses of calcium oxalate occur near the vascular bundles (2, 4).

Powdered plant material

The colour of the powder agrees with that of the leaves. The powder shows fragments of the epidermis with wavelike indentations irregular in form with generally elongated cells; large stomal openings of the anisocytic type; markedly elongated, narrow cells with only weakly undulated walls in the vascular areas and without marked indentations. The equifacial mesophyll comprises excretory vesicles, secretory cells, and idioblasts, as well as intermittent calcium oxalate druses, in the region of the vascular fascicles (2, 8).

Geographical distribution

Native to China, but grown as an ornamental shade tree in Australia, south-east Asia, Europe, Japan, and the United States of America (13, 6). It is commercially cultivated in France and the United States of America (2).

General identity tests

Macroscopic and microscopic examinations (2, 8). Thin-layer chromatographic analysis for the presence of the characteristic flavonoids, ginkgolides, and bilobalide (9); high-performance liquid chromatographic analysis for flavonoids (10), ginkgolides, and bilobalide (2); and gas–liquid chromatographic evaluation of ginkgolides and bilobalide (11).

Purity tests

Microbiology

The test for Salmonella spp. in Folium Ginkgo should be negative. The maximum acceptable limits of other microorganisms are as follows (1214). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for internal use: aerobic bacteria-not more than 105/g or ml; fungi-not more than 104/g or ml; enterobacteria and certain Gram-negative bacteria-not more than 103/g or ml; Escherichia coli-0/g or ml.

Foreign organic matter

Not more than 5% of twigs and not more than 2% of other foreign matter (15).

Total ash

Not more than 11% (15).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Folium Ginkgo is not more than 0.05 mg/kg (14). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (12), and guidelines for predicting dietary intake of pesticide residues (16).

Heavy metals

Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (12).

Radioactive residues

For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (12).

Other purity tests

Acid-insoluble ash, acid-insoluble extractive, chemical, and moisture tests to be established in accordance with national requirements.

Chemical assays

Flavonoids not less than 0.5% calculated as flavonol glycosides or 0.2–0.4% calculated as aglycones (17); also contains ginkgolides (0.06–0.23%) and bilobalide (up to 0.26%) (2, 17).

Qualitative and quantitative determination of flavonoid glycosides is carried out after hydrolysis to the aglycones kaempferol, quercetin, and isorhamnetin. The qualitative presence or absence of biflavones (17) is determined by highperformance liquid chromatography; and qualitative and quantitative determination of the diterpene ginkgolides and sesquiterpene bilobalide by high-performance liquid chromatography (2, 18) or gas–liquid chromatography (11).

Certain commercial products used for clinical and experimental biological studies, e.g. EGb 761 and LI 1370, do not contain biflavones.

Major chemical constituents

Folium Ginkgo contains a wide variety of phytochemicals, including alkanes, lipids, sterols, benzenoids, carotenoids, phenylpropanoids, carbohydrates, flavonoids, and terpenoids (18, 19). The major constituents are flavonoids of which mono-, di-, and tri-glycosides and coumaric acid esters that are based on the flavonols kaempferol and quercetin dominate. Lesser quantities of glycosides are derived from isorhamnetin, myricetin, and 3’-methylmyricetin. Nonglycosidic biflavonoids, catechins, and proanthocyanidins are also present (15). Characteristic constituents of this plant material are the unique diterpene lactones ginkgolides A, B, C, J, and M and the sesquiterpene lactone bilobalide (17). Representative structures of the major and characteristic constituents are presented below.

 

R1

R2

R3

R4

amentoflavone

O

OH

OH

H

bilobetin

OCH3

OH

OH

H

ginkgetin

OCH3

OCH3

OH

H

isoginkgetin

OCH3

OH

OCH3

H

5'-methoxybilobetin

OCH3

OH

OH

OCH3

sciadopitysin

OCH3

OCH3

OCH3

H

 

R

R'

R2

R3

 

ginkgolide A

H

H

H

OH

 

ginkgolide B

H

OH

H

OH

 

ginkgolide C

OH

H

OH

OH

O

ginkgolide J

H

H

OH

OH

 

ginkgolide M

OH

H

OH

H

 

Dosage forms

Standardized extracts (dry extracts from dried leaves, extracted with acetone and water, drug:extract ratio 35–67:1) contain 22–27% flavone glycosides and 5–7% terpene lactones, of which approximately 2.8–3.4% consists of ginkgolides A, B, and C and 2.6–3.2% bilobalide. The level of ginkgolic acids is below 5mg/kg. Coated tablets and solution for oral administration are prepared from standardized purified extracts (20, 21).

Medicinal uses

Uses supported by clinical data

Extracts as described above (Dosage forms) have been used for symptomatic treatment of mild to moderate cerebrovascular insufficiency (demential syndromes in primary degenerative dementia, vascular dementia, and mixed forms of both) with the following symptoms: memory deficit, disturbance in concentration, depressive emotional condition, dizziness, tinnitus, and headache (1, 3, 20–22). Such extracts are also used to improve pain-free walking distance in people with peripheral arterial occlusive disease such as intermittent claudication, Raynaud disease, acrocyanosis, and post-phlebitis syndrome, and to treat inner ear disorders such as tinnitus and vertigo of vascular and involutive origin (20, 23–27). Extracts and doses other than those described in Dosage forms and Posology are used for similar but milder indications (28, 29).

Uses described in pharmacopoeias and in traditional systems of medicine

None.

Uses described in folk medicine, not supported by experimental or clinical data

As a vermifuge, to induce labour, for the treatment of bronchitis, chronic rhinitis, chilblains, arthritis, and oedema (3, 5).

Pharmacology

Experimental pharmacology

Cerebrovascular insufficiency and peripheral vascular diseases

In vitro studies. A standardized extract of Ginkgo biloba (100µg/ml) did not produce isometrically recordable contractions in isolated rabbit aorta but did potentiate the contractile effect of norepinephrine (30). Higher concentrations (EC50≈ 1.0 mg/ml) produced a concentration-dependent contraction that could be antagonized by the α-adrenoceptor-blocking agent phentolamine (30). Both cocaine and desipramine, inhibitors of catecholamine re-uptake, potentiated the contractile effect of norepinephrine but inhibited the contractile effects of a standardized extract of G. biloba and tyramine (30). The results of these experiments indicate that the contractile action of G. biloba may be due to the release of catecholamines from endogenous tissue reserves, and this activity may explain some of the therapeutic effects of the drug in humans (e.g. improvement in cerebrovascular and peripheral vascular insufficiency) (1, 30). On the basis of experiments comparing the effects of an extract of G. biloba, phentolamine, propranolol, gallopamil, theophylline, and papaverine on the biphasic contractile response of norepinephrine in isolated rat aorta, researchers concluded that G. biloba had musculotropic action similar to that of papaverine (31). This activity was previously reported for the flavonoids quercetin, kaempferol, and isorhamnetin, isolated from the leaves of G. biloba (32). The flavonoids and papaverine both inhibit 3', 5' -cyclic-GMP phosphodiesterase, which in turn induces endothelium-dependent relaxation in isolated rabbit aorta by potentiating the effects of endothelium-derived relaxing factors (1).

In vitro studies have demonstrated that G. biloba extracts scavenge free radicals (33–37). Ginkgo biloba extracts have been reported to reduce free radicallipid peroxidation induced by NADPH-Fe3+ systems in rat microsomes (33), and to protect human liver microsomes from lipid peroxidation caused by ciclosporin A (34). The extract also inhibits the generation of reactive oxygen radicals in human leukocytes treated with phorbol myristate acetate (35). The antioxidant action of G. biloba extract may prolong the half-life of endotheliumderived relaxing factor by scavenging superoxide anions (36, 37). Both the flavonoid and terpenoid constituents of G. biloba appear to aid the free-radical scavenging activity of the drug (37).

Ginkgo biloba extract protected against brain tissue hypoxic damage in vitro. The ginkgolides and bilobalide were responsible for the antihypoxic activity of the extract (38, 39). Ginkgolides A and B have been shown to protect rat hippocampal neurons against ischaemic damage, which may be due to their ability to act as antagonists to receptors for platelet-activating factor (PAF) (40– 42).

In vivo studies. Oral administration of G. biloba extract protected rats against induced cerebral ischaemia (43–45). Intravenous perfusion of a G. biloba extract prevented the development of multiple cerebral infarction in dogs injected with fragments of an autologous clot into a common carotid artery (46). These data suggest that G. biloba extract, administered after clot formation, may have some beneficial effects on acute cerebral infarction or ischaemia caused by embolism (1). Other experiments demonstrated that animals treated with G. biloba extract survived under hypoxic conditions longer than did untreated controls (47, 48). Longer survival was due not only to significant improvements in cerebral blood flow, but also to an increase in the level of glucose and ATP (44, 48–50). Other studies have shown that a G. biloba extract devoid of ginkgolides but containing bilobalide had protective activity when administered intraperitoneally to mice with induced hypobaric hypoxia (51, 52). Intravenous infusion of G. biloba extract significantly increased pial arteriolar diameter in cats (53) and improved cerebral blood flow in rats (53). The active constituents of G. biloba responsible for increasing cerebral blood flow appeared to be the non-flavonoid compounds (54); ginkgolide B may be responsible for this action owing to its PAF-antagonist activity (55, 56). Furthermore, intravenous administration of a standardized G. biloba extract and ginkgolide B to rats showed that the extract, but not ginkgolide B, decreased the brain's use of glucose (57).

The constituents of G. biloba responsible for its anti-ischaemic activity remain undefined. The flavonoids, ginkgolides, and bilobalide have all been suggested, but it is possible that other constituents may be responsible.

An extract of G. biloba was effective in the in vivo treatment of cerebral oedema, a condition of excessive hydration of neural tissues owing to damage by neurotoxic agents (such as triethyltin) or trauma (58–60). Bilobalide appeared to play a significant role in the antioedema effect (61, 62). Oral or subcutaneous administration of an extract of G. biloba to rats with acute and chronic phases of adriamycin-induced paw inflammation partially reversed the increase in brain water, sodium, and calcium and the decrease in brain potassium associated with sodium arachidonate-induced cerebral infarction (63).

Mice treated with a standardized extract of G. biloba (100 mg/kg, orally for 4–8 weeks) showed improved memory and learning during appetitive operant conditioning (64).

Vestibular and auditory effects

Ginkgo biloba extract improved the sum of action potentials in the cochlea and acoustic nerve in cases of acoustically produced sound trauma in guinea-pigs (1, 65). The mechanism reduced the metabolic damage to the cochlea. Oral or parenteral administration of a standardized G. biloba extract to mice (2mg/kg) improved the ultrastructure qualities of vestibular sensory epithelia when the tissue was fixed by vascular perfusion (66). Improvement was due to the effects of the drug on capillary permeability and general microcirculation (1, 66).

Positive effects on vestibular compensation were observed after administration of G. biloba extract (50 mg/kg intraperitoneally) to rats and cats that had undergone unilateral vestibular neurectomy (67, 68).

Antagonism of platelet-activating factor (PAF)

The ginkgolides, and in particular ginkgolide B, are known antagonists of PAF (69–73). PAF is a potent inducer of platelet aggregation, neutrophil degranulation, and oxygen radical production leading to increased microvascular permeability and bronchoconstriction. Intravenous injections of PAF induced transient thrombocytopenia in guinea-pigs, which was accompanied by nonhistamine- dependent bronchospasm (69, 70). Ginkgolide B has been shown to be a potent inhibitor of PAF-induced thrombocytopenia and bronchoconstriction (71, 72). PAF or ovalbumin-induced bronchoconstriction in sensitized guinea-pigs was inhibited by an intravenous injection of ginkgolide B (1–3mg/kg) 5 minutes prior to challenge (73).

Clinical pharmacology

Cerebral insufficiency

Cerebral insufficiency is an inexact term to describe a collection of symptoms associated with dementia (21, 22). In dementia owing to degeneration with neuronal loss and impaired neurotransmission, decline of intellectual function is associated with disturbances in the supply of oxygen and glucose. In clinical studies G. biloba effectively managed symptoms of cerebral insufficiency including difficulty in concentration and memory, absent-mindedness, confusion, lack of energy, tiredness, decreased physical performance, depressive mood, anxiety, dizziness, tinnitus, and headache (2022). Several mechanisms of action of G. biloba have been described: effects on blood circulation such as the vasoregulating activity of arteries, capillaries, veins (increased blood flow); rheological effects (decreased viscosity, by PAF-receptor antagonism); metabolic changes such as increased tolerance to anoxia; beneficial influence on neurotransmitter disturbances; and prevention of damage to membranes by free radicals (22). Treatment of humans with G. biloba extract has been shown to improve global and local cerebral blood flow and microcirculation (74–76), to protect against hypoxia (77), to improve blood rheology, including inhibition of platelet aggregation (74, 78–81), to improve tissue metabolism (82), and to reduce capillary permeability (83).

A critical review of 40 published clinical trials (up to the end of 1990) using an orally administered G. biloba extract in the treatment of cerebral insufficiency concluded that only eight of the studies were well performed (21, 22). Almost all trials reported at least a partially positive response at dosages of 120–160mg a day (standardized extract) and treatment for at least 4–6 weeks (21, 22). In a comparison of G. biloba with published trials using co-dergocrine (dihydroergotoxine), a mixture of ergoloid mesilates used for the same purpose, both G. biloba extract and co-dergocrine showed similar efficacy. A direct comparison of 120mg of G. biloba standardized extract and 4.5mg codergocrine showed similar improvements in both groups after 6 weeks (84).

A meta-analysis of 11 placebo-controlled, randomized double-blind studies in elderly patients given G. biloba extract (150 mg orally per day) for cerebral insufficiency concluded that eight studies were well performed (85). Significant differences were found for all analysed single symptoms, indicating the superiority of the drug in comparison with the placebo. Analysis of the total score of clinical symptoms indicated that seven studies confirmed the effectiveness of G. biloba extract, while one study was inconclusive (85).

Peripheral arterial occlusive disease

The effectiveness of G. biloba extract in the treatment of intermittent claudication (peripheral arterial occlusive disease Fontaine stage II), as compared with a placebo, was demonstrated in placebo-controlled, double-blind clinical trials by a statistically significant increase in walking distance (1, 23, 24). Sixty patients with peripheral arterial occlusive disease in Fontaine stage IIb who were treated with the drug (120–160mg for 24 weeks) and underwent physical training also clearly increased their walking distance (25).

Out of 15 controlled trials (up to the end of 1990) only two (23, 24) were of acceptable quality (22–24). The results of both studies were positive and showed an increase in walking distance in patients with intermittent claudication after 6 months (23), and an improvement of pain at rest in patients treated with 200 mg of G. biloba extract for 8 weeks (24).

After meta-analysis of five placebo-controlled clinical trials (up to the end of 1991) of G. biloba extract in patients with peripheral arterial disease, investigators concluded that the extract exerted a highly significant therapeutic effect (26).

Vertigo and tinnitus

Ginkgo biloba extracts have been used clinically in the treatment of inner ear disorders such as hearing loss, vertigo, and tinnitus. In a placebo-controlled, double-blind study of 68 patients with vertiginous syndrome of recent onset, treatment with G. biloba extract (120–160mg daily, for 4–12 weeks) produced a statistically significant improvement as compared with the placebo group (27).

The results of clinical studies on the treatment of tinnitus have been contradictory. At least six clinical studies have assessed the effectiveness of G. biloba extract for the treatment of tinnitus. Three studies reported positive results (86, 87, 88). One multicentre, randomized, double-blind, 13-month study of 103 patients with tinnitus showed that all patients improved, irrespective of the prognostic factor, when treated with G. biloba extract (160mg/day for 3 months) (86). Three other clinical trials reported negative outcomes (89–91). Statistical analysis of an open study (80 patients) without placebo, coupled with a double-blind, placebo-controlled part (21 patients), demonstrated that a concentrated G. biloba extract (29.2 mg/day for 2 weeks) had no effect on tinnitus (91).

Contraindications

Hypersensitivity to G. biloba preparations (20).

Warnings

No information available.

Precautions

Carcinogenesis, mutagenesis, impairment of fertility

Investigations with G. biloba extracts have shown no effects that were mutagenic, carcinogenic, or toxic to reproduction (20).

Pregnancy: non-teratogenic effects

The safety of Folium Ginkgo for use during pregnancy has not been established.

Nursing mothers

Excretion of Folium Ginkgo into breast milk and its effects on the newborn have not been established.

Other precautions

No information is available concerning general precautions or drug interactions, drug and laboratory test interactions, teratogenic effects on pregnancy, or paediatric use.

Adverse reactions

Headaches, gastrointestinal disturbances, and allergic skin reactions are possible adverse effects (20).

Posology

Dried extract (as described in Dosage forms), 120–240mg daily in 2 or 3 divided doses (2); 40 mg extract is equivalent to 1.4–2.7 g leaves (20). Fluid extract (1: 1), 0.5 ml 3 times a day (1, 2).

References

1. DeFeudis FV. Ginkgo biloba extract (egb 761): pharmacological activities and clinical applications. Paris, Elsevier, Editions Scientifiques, 1991:1187.

2. Hänsel R et al., eds. Hagers Handbuch der pharmazeutischen Praxis, Vol. 6, 5th ed. Berlin, Springer-Verlag, 1994.

3. Squires R. Ginkgo biloba. Australian traditional medicine society (ATOMS), 1995:9–14.

4. Huh H, Staba EJ. The botany and chemistry of Ginkgo biloba L. Journal of herbs, spices and medicinal plants, 1992, 1:91–124.

5. Farnsworth NR, ed. NAPRALERT database. University of Illinois at Chicago, IL, August 8, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).

6. Keys JD. Chinese herbs, their botany, chemistry and pharmacodynamics. Rutland, VT, CE Tuttle, 1976:30–31.

7. Pharmacopoeia of the People's Republic of China (English ed.). Guangzhou, Guangdong Science and Technology Press, 1992:64.

8. Melzheimer V. Ginkgo biloba L. aus Sicht der systematischen und angewandten Botanik. Pharmazie in unserer Zeit, 1992, 21:206–214.

9. Van Beek TA, Lelyveld GP. Thin layer chromatography of bilobalide and ginkgolides A, B, C and J on sodium acetate impregnated silica gel. Phytochemical analysis, 1993, 4:109–114.

10. Hasler A, Meier B, Sticher O. Identification and determination of the flavonoids from Ginkgo biloba by HPLC. Journal of chromatography, 1992, 605:41–48.

11. Hasler A, Meier B. Determination of terpenes from Ginkgo biloba by GLC. Pharmacy and pharmacology letters, 1992, 2:187–190.

12. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.

13. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.

14. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.

15. Sticher O. Biochemical, pharmaceutical and medical perspectives of Ginkgo preparations. In: New Drug Development from Herbal Medicines in Neuropsychopharmacology. Symposium of the XIXth CINP Congress, Washington, DC, June 27–July 1, 1994.

16. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).

17. Sticher O. Quality of Ginkgo preparations. Planta medica, 1993, 59:2–11.

18. Van Beek TA et al. Determination of ginkgolides and bilobalide in Ginkgo biloba leaves and phytochemicals. Journal of chromatography, 1991, 543:375–387.

19. Hasler A et al. Complex flavonol glycosides from the leaves of Ginkgo biloba. Phytochemistry, 1992, 31:1391.

20. German Commission E monograph, Trockenextrakt (35–67: 1) aus Ginkgo-biloba- Blättern Extrakt mit Aceton-Wasser. Bundesanzeiger, 1994, 46:7361–7362.

21. Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340:1136–1139.

22. Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. British journal of clinical pharmacology, 1992, 34:352–358.

23. Bauer U. Six month double-blind randomized clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency. Arzneimittel-Forschung, 1984, 34:716–720.

24. Saudreau F, Serise JM, Pillet J. Efficacité de l'extrait de Ginkgo biloba dans le traitement des artériopathies obliterantes chroniques des membres inferieurs au stade III de la classification de Fontaine. Journal malade vasculare, 1989, 14:177– 182.

25. Blume J et al. Placebokontrollierte Doppelblindstudie zur Wirksamkeit von Ginkgo biloba-Spezialextrakt EGb 761 bei austrainierten Patienten mit Claudicatio intermittens. VASA, 1996, 2:1–11.

26. Schneider B. Ginkgo biloba Extrakt bei peripheren arteriellen Verschlußkrankheiten. Arzneimittel-Forschung, 1992, 42:428–436.

27. Haguenauer JP et al. Traitement des troubles de l'equilibre par l'extrait de Ginkgo biloba. Presse medicale, 1986, 15:1569–1572.

28. Coeur et circulation, 02.97.0 Troubles de l'artériosclérose. IKS monthly bulletin, 1994, 6:532–533.

29. Kade F, Miller W. Dose-dependent effects of Ginkgo biloba extraction on cerebral, mental and physical efficiency: a placebo controlled double blind study. British journal of clinical research, 1993, 4:97–103.

30. Auguet M, DeFeudis FV, Clostre F. Effects of Ginkgo biloba on arterial smooth muscle responses to vasoactive stimuli. General pharmacology, 1982, 13:169–171, 225– 230.

31. Auguet M, Clostre F. Effects of an extract of Ginkgo biloba and diverse substances on the phasic and tonic components of the contraction of an isolated rabbit aorta. General pharmacology, 1983, 14:277–280.

32. Peter H, Fisel J, Weisser W. Zur Pharmakologie der Wirkstoffe aus Ginkgo biloba. Arzneimittel-Forschung, 1966, 16:719–725.

33. Pincemail J et al. In: Farkas L, Gabor M, Kallay F, eds. Flavonoids and bioflavonoids. Szeged, Hungary, 1985:423.

34. Barth SA et al. Influences of Ginkgo biloba on cyclosporin induced lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and Nacetylcysteine. Biochemical pharmacology, 1991, 41:1521–1526.

35. Pincemail J et al. Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes. Experientia, 1987, 43:181–184.

36. Pincemail J, Dupuis M, Nasr C. Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract. Experientia, 1989, 45:708– 712.

37. Robak J, Gryglewski RJ. Flavonoids are scavengers of superoxide anions. Biochemical pharmacology, 1988, 37:837–841.

38. Oberpichler H et al. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacological research communications, 1988, 20:349–352.

39. Krieglstein J. Neuroprotective effects of Ginkgo biloba constituents. European journal of pharmaceutical sciences, 1995, 3:39–48.

40. Braquet P. The ginkgolides: potent platelet-activating factor antagonists isolated from Ginkgo biloba L.: chemistry, pharmacology and clinical application. Drugs of the future, 1987, 12:643–648.

41. Oberpichler H. PAF-antagonist ginkgolide B reduces postischemic neuronal damage in rat brain hippocampus. Journal of cerebral blood flow and metabolism, 1990, 10:133– 135.

42. Prehn JHM, Krieglstein J. Platelet-activating factor antagonists reduce excitotoxic damage in cultured neurons from embryonic chick telencephalon and protect the rat hippocampus and neocortex from ischemic injury in vivo. Journal of neuroscience research, 1993, 34:179–188.

43. Larssen RG, Dupeyron JP, Boulu RG. Modèles d'ischémie cérébrale expérimentale par microsphères chez le rat. Étude de l'effet de deux extraits de Ginkgo biloba et du naftidrofuryl. Thérapie, 1978, 33:651–660.

44. Rapin JR, Le Poncin-Lafitte M. Consommation cérébrale du glucose. Effet de l'extrait de Ginkgo biloba. Presse medica, 1986, 15:1494–1497.

45. Le Poncin-Lafitte MC, Rapin J, Rapin JR. Effects of Ginkgo biloba on changes induced by quantitative cerebral microembolization in rats. Archives of international pharmacodynamics, 1980, 243:236–244.

46. Cahn J. Effects of Ginkgo biloba extract (GBE) on the acute phase of cerebral ischaemia due to embolisms. In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment. London, John Libbey, 1985:43–49.

47. Chatterjee SS. Effects of Ginkgo biloba extract on cerebral metabolic processes. In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment. London, John Libby, 1985:5–14.

48. Karcher L, Zagermann P, Krieglstein J. Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia. Naunyn-Schmiedeberg's archives of pharmacology, 1984, 327:31–35.

49. Le Poncin-Lafitte M et al. Ischémie cérébrale après ligature non simultanèe des artères carotides chez le rat: effet de l'extrait de Ginkgo biloba. Semaine hopitale Paris, 1982, 58:403–406.

50. Iliff LD, Auer LM. The effect of intravenous infusion of Tebonin (Ginkgo biloba) on pial arteries in cats. Journal of neurosurgical science, 1982, 27:227–231.

51. Duverger D. Anoxie hypobare chez la souris avec les différents extraits de Ginkgo biloba. Le Plessis Robinson, France, Institut Henri-Beaufour, 1989 (Report no. 1116/89/DD/HK).

52. Duverger D. Anoxie hypobare chez la souris avec l'un des constituants de l'EGB:le HE 134. Le Plessis Robinson, France, Institut Henri-Beaufour, 1990 (Report no. 1182/90/DD/HK).

53. Krieglstein J, Beck T, Seibert A. Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. Life sciences, 1986, 39:2327–2334.

54. Beck T et al. Comparative study on the effects of two extract fractions of Ginkgo biloba on local cerebral blood flow and on brain energy metabolism in the rat under hypoxia. In: Krieglstein J, ed. Pharmacology of cerebral ischemia. Amsterdam, Elsevier, 1986:345–350.

55. Krieglstein J, Oberpichler H. Ginkgo biloba und Hirnleistungsstörungen. Pharmazeutische Zeitung, 1989, 13:2279–2289.

56. Oberpichler H et al. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacology research communications, 1988, 20:349– 352.

57. Lamor Y et al. Effects of ginkgolide B and Ginkgo biloba extract on local cerebral glucose utilization in the awake adult rat. Drug development research, 1991, 23:219– 225.

58. Chatterjee SS, Gabard B. Effect of an extract of Ginkgo biloba on experimental neurotoxicity. Archives of pharmacology, 1984, 325(Suppl.), Abstr. 327.

59. Otani M et al. Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral oedema. Acta neuropathology, 1986, 69:54–65.

60. Borzeix MG. Effects of Ginkgo biloba extract on two types of cerebral oedema. In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment. London, John Libbey, 1985:51–56.

61. Chatterjee SS, Gabard BL, Jaggy HEW. Pharmaceutical compositions containing bilobalide for the treatment of neuropathies. US Patent no. 4,571,407 (Feb 18, 1986).

62. Sancesario G, Kreutzberg GW. Stimulation of astrocytes affects cytotoxic brain oedema. Acta neuropathology, 1986, 72:3–14.

63. DeFeudis FV et al. Some in vitro and in vivo actions of an extract of Ginkgo biloba (GBE 761). In: Agnoli A et al., eds. Effects of Ginkgo biloba extract on organic cerebral impairment. London, John Libbey, 1985:17–29.

64. Winter E. Effects of an extract of Ginkgo biloba on learning and memory in mice. Pharmacology, biochemistry and behavior, 1991, 38:109–114.

65. Stange VG et al. Adaptationsverhalten peripherer und zentraler akustischer Reizantworten des Meerschweinchens unter dem Einfluss verschiedener Fraktionen eines Extraktes aus Ginkgo biloba. Arzneimittel-Forschung, 1976, 26:367–374.

66. Raymond J. Effets de l'extrait de Ginkgo biloba sur la préservation morphologique des épithéliums sensoriels vestibulaires chez la souris. Presse médicale, 1986, 15:1484– 1487.

67. Denise P, Bustany P. The effect of Ginkgo biloba (EGb 761) on central compensation of a total unilateral peripheral vestibular deficit in the rat. In: Lacour M et al., eds. Vestibular compensation: facts, theories and clinical perspectives. Paris, Elsevier, 1989:201– 208.

68. Lacour M, Ez-Zaher L, Raymond J. Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761). Pharmacology, biochemistry and behavior, 1991, 40:367–379.

69. Vargaftig BB et al. Platelet-activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives. European journal of pharmacology, 1982, 65:185–192.

70. Vargaftig BB, Benveniste J. Platelet-activating factor today. Trends in pharmacological sciences, 1983, 4:341–343.

71. Desquand S et al. Interference of BN 52021 (ginkgolide B) with the bronchopulmonary effects of PAF-acether in the guinea-pig. European journal of pharmacology, 1986, 127:83–95.

72. Desquand S, Vargaftig BB. Interference of the PAF-acether antagonist BN 52021 in bronchopulmonary anaphylaxis. Can a case be made for a role for PAF-acether in bronchopulmonary anaphylaxis in the guinea-pig? In: Braquet P, ed. Ginkgolides, Vol. 1. Barcelona, JR Prous, 1988:271–281.

73. Braquet P et al. Involvement of platelet activating factor in respiratory anaphylaxis, demonstrated by PAF-acether inhibitor BN 52021. Lancet, 1985, i:1501.

74. Költringer P et al. Die Mikrozirkulation und Viskoelastizität des Vollblutes unter Ginkgo biloba extrakt. Eine plazebokontrollierte, randomisierte Doppelblind-Studie. Perfusion, 1989, 1:28–30.

75. Költringer P et al. Mikrozirkulation unter parenteraler Ginkgo biloba Extrakt- Therapie. Wiener Medizinische Wochenschrift, 1989, 101:198–200.

76. Jung F et al. Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers. Arzneimittel-Forschung, 1990, 40:589–593.

77. Schaffler K, Reeh PW. Doppelblindstudie zur hypoxieprotektiven Wirkung eines standardisierten Ginkgo-biloba-Präparates nach Mehrfachverabreichung an gesunden Probanden. Arzneimittel-Forschung, 1985, 35:1283–1286.

78. Hofferberth B. Simultanerfassung elektrophysiologischer, psychometrischer und rheologischer Parameter bei Patienten mit hirnorganischem Psychosyndrom und erhöhtem Gefässrisiko-Eine Placebo-kontrollierte Doppelblindstudie mit Ginkgo biloba-Extrakt EGB 761. In: Stodtmeister R, Pillunat LE, eds. Mikrozirkulation in Gehirn und Sinnesorganen. Stuttgart, Ferdinand Enke, 1991:64–74.

79. Witte S. Therapeutical aspects of Ginkgo biloba flavone glucosides in the context of increased blood viscosity. Clinical hemorheology, 1989, 9:323–326.

80. Artmann GM, Schikarski C. Ginkgo biloba extract (EGb 761) protects red blood cells from oxidative damage. Clinical hemorheology, 1993, 13:529–539.

81. Ernst E, Marshall M. Der Effekt von Ginkgo-biloba-Spezialextrakt EGb 761 auf die Leukozytenfilterabilität-Eine Pilotstudie. Perfusion, 1992, 8:241–244.

82. Rudofsky G. Wirkung von Ginkgo-biloba-extrakt bei arterieller Verschlusskrankheit. Fortschritte der Medizin, 1987, 105:397–400.

83. Lagrue G, et al. Oedèmes cycliques idiopathiques. Rôle de l'hyperperméabilité capillaire et correction par l'extrait de Ginkgo biloba. Presse médicale, 1986, 15:1550– 1553.

84. Gerhardt G, Rogalla K, Jaeger J. Medikamentöse Therapie von Hirnleistungsstörungen. Randomisierte Vergleichsstudie mit Dihydroergotoxin und Ginkgo biloba- Extrakt. Fortschritte der Medizin, 1990, 108:384–388.

85. Hopfenmüller W. Nachweis der therapeutischen Wirksamkeit eines Ginkgo biloba Spezialextraktes. Arzneimittel-Forschung, 1994, 44:1005–1013.

86. Meyer B. Etude multicentrique randomisée a double insu face au placebo du traitement des acouphènes par l'extrait de Ginkgo biloba. Presse medicale, 1986, 15:1562–1564.

87. Sprenger FH. Gute Therapieergebnisse mit Ginkgo biloba. Ärztliche Praxis, 1986, 12:938–940.

88. Witt U. Low power laser und Ginkgo-Extrakte als Kombinationstherapie. Hamburg, Germany (unpublished document; available through NAPRALERT, see reference 5).

89. Coles RRA. Trial of an extract of Ginkgo biloba (EGB) for tinnitus and hearing loss. Clinical otolaryngology, 1988, 13:501–504.

90. Fucci JM et al. Effects of Ginkgo biloba extract on tinnitus: a double blind study. St. Petersberg, FL, Association for Research in Otolaryngology, 1991.

91. Holgers KM, Axelson A, Pringle I. Ginkgo biloba extract for the treatment of tinnitus. Audiology, 1994, 33:85–92.

 

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