- Clinical data 90%
- Efficacy 80%
- Security 70%
- Toxicity 30%
Pterophyllus salisburiensis Nelson, Salisburia adiantifolia Smith, Salisburia macrophylla C. Koch.
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.
Major chemical constituents
Folium Ginkgo contains a wide variety of phytochemicals, including alkanes, lipids, sterols, benzenoids, carotenoids, phenylpropanoids, carbohydrates, flavonoids, and terpenoids. 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. Characteristic constituents of this plant material are the unique diterpene lactones ginkgolides A, B, C, J, and M and the sesquiterpene lactone bilobalide.
Medicinal uses of Ginkgo biloba
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. 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. Extracts and doses other than those described in Dosage forms and Posology are used for similar but milder indications.
Uses described in pharmacopoeias and in traditional systems of medicine
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.
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. Higher concentrations (EC50 1.0 mg/ml) produced a concentration-dependent contraction that could be antagonized by the α-adrenoceptor-blocking agent phentolamine. Both cocaine and desipramine, inhibitors of catecholamine re-uptake, potentiated the contractile effect of norepinephrine but inhibited the contractile effects of astandardized extract of G. biloba and tyramine. 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). 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. This activity was previously reported for the flavonoids quercetin, kaempferol, and isorhamnetin, isolated from the leaves of G. biloba. 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. In vitro studies have demonstrated that G. biloba extracts scavenge free radicals. Ginkgo biloba extracts have been reported to reduce free radicallipid peroxidation induced by NADPH-Fe3 systems in rat microsomes, and to protect human liver microsomes from lipid peroxidation caused by ciclosporin A. The extract also inhibits the generation of reactive oxygen radicals in human leukocytes treated with phorbol myristate acetate. The antioxidant action of G. biloba extract may prolong the half-life of endotheliumderived relaxing factor by scavenging superoxide anions.
Both the flavonoid and terpenoid constituents of G. biloba appear to aid the free-radical scavenging activity of the drug. Ginkgo biloba extract protected against brain tissue hypoxic damage in vitro.
The ginkgolides and bilobalide were responsible for the antihypoxic activity of the extract. 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).
In vivo studies. Oral administration of G. biloba extract protected rats against induced cerebral ischaemia. 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. 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. Other experiments demonstrated that animals treated with G. biloba extract survived under hypoxic conditions longer than did untreated controls. 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. 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. Intravenous infusion of G. biloba extract significantly increased pial arteriolar diameter in cats and improved cerebral blood flow in rats. The active constituents of G. biloba responsible for increasing cerebral blood flow appeared to be the non-flavonoid compounds; ginkgolide B may be responsible for this action owing to its PAF-antagonist activity. 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. 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. Bilobalide appeared to play a significant role in the antioedema effect. 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.
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.
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. 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. 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.
Antagonism of platelet-activating factor (PAF) The ginkgolides, and in particular ginkgolide B, are known antagonists of PAF. 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-dependentbronchospasm. Ginkgolide B has been shown to be a potent inhibitor of PAF-induced thrombocytopenia and bronchoconstriction. 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.
Cerebral insufficiency is an inexact term to describe a collection of symptoms associated with dementia. 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. 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. Treatment of humans with G. biloba extract has been shown to improve global and local cerebral blood flow and microcirculation, to protect against hypoxia, to improve blood rheology, including inhibition of platelet aggregation, to improve tissue metabolism, and to reduce capillary permeability. 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. 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. 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. 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. 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.
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. 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. Out of 15 controlled trials (up to the end of 1990) only two (23, 24) were of acceptable quality. The results of both studies were positive and showed an increase in walking distance in patients with intermittent claudication after 6 months, and an improvement of pain at rest in patients treated with 200 mg of G. biloba extract for 8 weeks. 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.
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.
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. 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). Three other clinical trials reported negative outcomes. 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.
Hypersensitivity to G. biloba preparations.
No information available.
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