Articles

Ginkgo biloba L.

 

Last updated: 13 May 2016

Scientific Name

Ginkgo biloba L.

Synonyms

Ginkgo macrophylla K. Koch, Pterophyllus salisburiensis J. Nelson, Salisburia adiantifolia Sm., Salisburia biloba (L.) Hoffmanns., Salisburia ginkgo Rich., Salisburia macrophylla Reyn. [1]

Vernacular Name

English Ginko, maidenhair tree [2]
China Bai guo, yin kuo, pai kuo, yin hsing, yin xing [2]
Japan Ichô ka, icho (ichô=duck’s foot), haburugii (Okinawa) [2].

Geographical Distributions

No documentation.

Botanical Description

Ginkgo biloba is a member of the Ginkgoaceae family. It is a deciduous trees that can grow up to 40 m tall. [3]

The trunk diameter at breast height can be measured up to 4 m. The bark is usually light gray or grayish brown in colour, longitudinally fissured especially on old trees; crown conical initially, finally broadly ovoid; long branchlets pale brownish yellow initially, finally gray, internodes (1-) 1.5-4 cm; short branchlets blackish gray. [3]

The leaves are dense and have irregularly elliptic leaf scars. The winter buds are yellowish brown in colour with, ovate shape. Leaves with petiole (3-)5-8(-10) cm; blade pale green, turning bright yellow in autumn, to 13 × 8(-15) cm on young trees but usually 5-8 cm wide, those on long branchlets divided by a deep, apical sinus into 2 lobes each further dissected, those on short branchlets with undulate distal and margin notched apex. Pollen cones ivory colored, 1.2-2.2 cm; pollen sacs boat-shaped, with widely gaping slit. [3]

The seeds are elliptic, narrowly obovoid, ovoid, or subglobose, 2.5-3.5 × 1.6-2.2 cm; sarcotesta yellow, or orange-yellow glaucous, with rancid odor when ripe; sclerotesta white, with 2 or 3 longitudinal ridges; endotesta pale reddish brown. Pollination Mar-Apr, seed maturity Sep-Oct. [3]

Cultivation

No documentation

Chemical Constituent

G. biloba has been reported to contain terpene lactones (e.g. ginkgolides A, ginkgolides B, ginkgolides C, and bilobalide) and flavonoids (e.g. myricetin, quercetin, proanthocyanidins, and catechins). [4]

Plant Part Used

Leaves, roots, and seeds. [3]

Traditional Use

G. biloba leaves are medicinal and used for pesticides, the roots are used to cure leucorrhea. [3]

Preclinical Data

Pharmacology

Antioxidant avtivity

The main active components of G. biloba include the flavoglycosides, and terpene lactones. These compounds act as strong free radical scavengers or antioxidants which can be attributed to many of ginkgo’s positive effect on body systems. [5][6][7] Ginkgo’s ability to decrease the loss of cell viability due to oxidative stress in many areas of the body is the main pharmacological property of the therapeutic efficacy of this dietary supplement. [8] Studies have reported that constituents in ginkgo may actually protect the brain neurons from oxidation and subsequent damaging free radicals, decreasing post-ischemic effects, and diseases such as Alzheimer’s disease. [9][10][11] It is also postulated that ginkgo’s positive effects against cardiac ischemia-reperfusion injury depend on its antioxidant properties. [12][13][14]

Antioxidant effects of G. biloba are also reported to decrease the damaging effects of radiation and chemotherapy. [15] The antioxidant activity of ginkgo was reported to decrease the negative effects of clastogenic factors created by radiation exposure. [16] Clastogenic factors are bio-markers of oxidative stress found in the plasma of irradiated persons, either accidentally or therapeutically, and cause the development of latent effects associated with damaging radiation. The negative effects of cyclosporin A on lipid peroxidation in human liver microsomes was decreased with the administration of a standardized ginkgo preparation during in vitro testing, suggesting that ginkgo might be able to prevent radical mediated damage to human membranes caused by this agent. [17] It should be noted that also in this study, vitamin E almost completely inhibited the lipid peroxidation caused by cyclosporin A. [17]

PAF antagonism

G. biloba is also reported to inhibit platelet activating factor (PAF), reducing the adhesive nature of platelets possibly through competitive binding [18]. One of the components of ginkgo, ginkgolide B, is a potent platelet-activating factor (PAF) antagonist [19]. This action has been reported to contribute to ginkgo’s influence on increased cerebral and peripheral blood flow, improvement of delivery of nutrients to the brain, oxygenation of the tissues, and its positive effects in asthma and cardiovascular protection. [20][21] Free radicals and platelet activating factor (PAF) have been implicated as important mediators in neuronal injury after cerebral ischemia-reperfusion and, particularly, in postischemic hypoperfusion [22]. The PAF and antioxidant properties of ginkgo have also been reported useful in acute pancreatitis [23]. Ginkgo may foster vasodilation by stimulating endothelium releasing factor and prostacyclin [24]. It may also stimulate venous tone and improve the clearance of hemotoxins during ischemic episodes [25].

Senile dementia and Alzheimer’s disease

Modern research has helped to provide a better understanding of biochemical events that occur with the disease process of Alzheimer’s, including theories of the accumulation of beta-amyloid (Abeta)-derived peptides and free radical damage in the involvement of the destruction of neuronal cells [10][26]. G. biloba has been reported effective in decreasing the toxicity induced by (Abeta)-derived peptides (Abeta25-35, Abeta1-40 and Abeta1-42) on hippocampal primary cultured cells in vitro and also, as stated above, in reducing the damaging oxidative stress to neuronal cells, both of which have been reported to increase the probability of developing senile dementia and Alzheimer’s disease [27][28].

General memory and learning impairment

G. biloba has been reported in laboratory animals to increase learning and other cognitive behaviours. [29][30][31] Also, studies in humans have reported positive effects on age-associated memory impairment and learning along with an increase in attention. [32][33] Although the terpene fraction of ginkgo, which contains the ginkgolides, may contribute to the neuroprotective properties of the leaf, it is also likely that the flavonoid fraction, containing free radical scavengers, is also important in this respect. Taken together, the evidence suggests that Ginkgo biloba extracts are worthy of further investigation as potential neuroprotective agents. Ginkgo may also normalize acetylcholine receptors and, therefore, improve cholinergic function. [34]

Depression

G. biloba’s use in depression may be in part due to its increase in cerebral blood flow [35]. Ginkgo has been reported in laboratory studies to have monoamine oxidase inhibiting (MAOI) effects (both MAO-A and -B types were inhibited to a similar extent). [36] The authors have postulated that ginkgo’s MAOI ability may be one mechanism for its reported anti-stress and antidepressant uses. Recent studies (both in humans and laboratory animals), however, have reported that ginkgo administration does not produce significant changes in brain MAO A or MAO B, suggesting that mechanisms other than MAO inhibition need to be considered as mediating some of its antidepressant effects. [37][38][39]

Asthma

G. biloba has been used in China for thousands of years in the treatment of asthma. Ginkgo, a PAF inhibitor, can inhibit inflammatory pathways that are implicated in asthmatic conditions, and has been reported beneficial in reducing antigen-induced lung anaphylaxis in laboratory animals. [40][41] Another in vitro study reported that ginkgolide B may have anti-inflammatory effects that are helpful in addition to other conventional therapies in controlling asthmatic patients. [42]

Toxicity

No documentation

Clinical Data

Clinical findings

Antioxidant effects

Also, due to the potent antioxidant activity of G. biloba, a clinical study reported statistically significant improvements in visual function in patients having macular degeneration, glaucoma cataracts, and retinal impairments. [43][44][45][46] Among the many clinical applications of ginkgo as an antioxidant are spinal cord injury, [47] lipid peroxidation pertaining to cholesterol metabolism including protection of HDL [48][49], cardiovascular protection including limiting oxidative stress in cardiovascular surgery [50][51], hepatoprotective effects [52][53], and in general to decrease the mitochondrial oxidative stresses that cause normal aging. [54]

Dementia and Alzheimer’s Disease

The efficacy of standardized G. biloba preparations in dementia of the Alzheimer type and multi-infarct dementia has been confirmed by many scientific studies in human subjects [38] although there are conflicting studies. [55][56][57][58] In 1994, a standardized dry extract of G. biloba leaves was approved by German health authorities for the treatment of primary degenerative dementia and vascular dementia. [59]

A randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 309 patients with mild to severe dementia including Alzheimer disease or multi-infarct dementia were placed on a standardized G. biloba preparation or placebo for 52 weeks. [60] From the initial 309 patients included in the study, 202 of these individuals provided data for statistical analysis. Although not as significant as expected, the standardized ginkgo preparation (40 mg three times a day) was reported safe and capable of stabilizing and improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. However, a recent 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of 214 subjects with dementia (either Alzheimer’s or vascular dementia) reported that treatment with the same standardized ginkgo preparation as above (either 2 tablets per day, total dosage either 240 or 160 mg/day or placebo for a total of 24 weeks) reported no advantage of using the ginkgo extract over placebo. [61]

General Memory and Learning Impairment

A study involving healthier individuals also questions the benefit of G. biloba for memory enhancement. This six-week randomized, double-blind, placebo-controlled, parallel-group trial involving 230 individuals older than 60 was designed to evaluate whether ginkgo could improve memory in this patient population. These individuals had to be in good health and needed a baseline Mini-Mental State Examination (MMSE) score greater than 26. They were then randomized to receive ginkgo, 40 mg, 3 times per day or matching placebo, 115 people in each group. Prior to beginning treatment and three days before completion of the six-week treatment program, each patient was evaluated by fifteen standard neuropsychological tests evaluating verbal and nonverbal learning and memory, attention and concentration, and naming and expressive language. Each participant completed a subjective self-report on memory and a companion completed a caregiver clinical global impression of change. The results of this study showed no improvement in the standard neuropsychological tests utilized and there was no difference between the groups in the self-reported memory function or in the global rating completed by their companion. [62]

A recent 6-week, double-blind, fixed-dose, placebo-controlled, parallel-group experimental study design was conducted to evaluate the effectiveness of ginkgo on cognitive and behavioral functioning. The individuals were given 180 mg of a standardized G. biloba extract or placebo daily for 6 weeks. This group exhibited significantly more improvement on a task assessing speed of processing abilities and memory as compared to participants who received placebo. [63]

Another double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-center trial of 256 healthy individuals was conducted to evaluate the effectiveness of ginkgo in combination with Panax ginseng (containing 60 mg standardized G. biloba and 100 mg standardized panax, either 1 capsule twice daily or 2 capsules in the am) on cognitive function [64]. The ginkgo/panax combination was found to significantly improve several different aspects of memory, including working and long-term memory. The memory enhancement was reported throughout the 12-week dosing period and also after a 2-week washout. A small multiple dose, placebo-controlled, double-blind, balanced-crossover study in young healthy subjects found that ginkgo modestly improved memory performance, but acute administration may have a negative effect on the speed of attention task performance, which is opposite to that seen previously following higher doses (greater than 120mg daily standardized) [65].

A 2009 selective review of 29 randomized controlled trials found that here is consistent evidence that chronic administration of G. biloba supplements improves selective attention, some executive processes and long-term memory for verbal and non-verbal material [66]. Also complexation of ginkgo with phosphatidylserine appears to potentiate the cognitive effects [67].

Intermittent Claudication/ Cardiovascular Effects

G. biloba has been reported useful in the treatment of peripheral occlusive arterial diseases (PAD) [68]. Studies have reported that ginkgo products produce a statistically significant and clinically relevant improvement of the walking performance in patients suffering from intermittent claudication [69][70][71]. Ginkgo has been studied and compared to trental, which is used for intermittent claudication and peripheral vascular disturbances [72]. In treadmill walking studies, ginkgo significantly increased pain-free walking distance [73][74]. Exercising regularly, stopping smoking, and limiting caffeine intake are also important in treating these conditions. Because of its ability to improve blood flow, ginkgo has been used for diabetic neuropathy, circulatory disorders, Raynaud’s Disease or cyanotic, or post-phlebitis pathologies [75].

A double-blind, placebo-controlled, parallel design trial with a 4-month duration found that in older adults with PAD, G. biloba produced a modest but insignificant increase in maximal treadmill walking time and flow-mediated vasodilation [76]. However, a 2009 Cochrane Database review looked at randomized controlled trials of ginkgo extract, irrespective of dosage, versus placebo in people with intermittent claudication. The authors concluded there is no evidence that ginkgo has a clinically significant benefit for patients with peripheral arterial disease. Further research needs to be performed in this area [77].

A small randomized trial found that G. biloba was effective in improving vascular endothelial function in early stage diabetic patients through decreasing the plasma level of von Willebrand Factor (vWF), raising the plasma nitric oxide (NO) levels and improving the endothelium dependent vascular dilating function. [78]

Tinnitus

G. biloba has traditionally been used in the treatment of tinnitus with positive results in both human and animal studies [78][79]. One multicenter, double-blind placebo controlled study of 103 patients with tinnitus reported positive benefits in the condition when using a ginkgo extract. However, some studies have shown contradictory results of ginkgo in the treatment of tinnitus, with no reported value in the condition versus placebo [80][81]. In these negative studies, three parameters should be taken into consideration that may have prognostic significance: chronicity, periodicity and uni- or bilateral nature of symptoms [82].

Depression

A study evaluated the effectiveness of G. biloba in forty depressed patients above the age of fifty who showed incomplete response to tricyclic or tetracyclic antidepressants. Patients in the treated group demonstrated significantly improved outcomes in depressive symptoms when compared to the placebo group [83][84].

Of interest, is that G. biloba products may be effective in reducing antidepressant-induced sexual dysfunction in humans [84][85][86]. It was reported to be 84% effective in treating antidepressant-induced sexual dysfunction predominately caused by selective serotonin reuptake inhibitors. The authors presumed the effectiveness was due to such pharmacological mechanisms as effects on platelet activating factor, prostaglandin inhibition, peripheral vasodilatation, and central serotonin and norepinephrine receptor factor modulation [84].

Asthma

In one study, clinical symptoms and pulmonary functions of asthma patients were improved in contrast to placebo, where the G. biloba product significantly reduced airway hyper-reactivity [87].

A clinical study found that G. biloba may decrease the activation of PKCalpha in inflammatory cells and thereby decrease the IL-5 level in induced sputum, allowing ginkgo to be used in conjunction with glucocorticosteroid therapy for asthma [88].

PMS

G. biloba has also been reported in clinical studies to help decrease the symptoms of PMS. A standardized extract of gingko was reported useful in a placebo controlled, multicenter, double blind study in treating congestive symptoms of PMS [89]. The authors reported that the ginkgo preparation was effective against the congestive symptoms of PMS, particularly breast symptoms and emotional disturbances. Another randomized, placebo-controlled study in 85 women with PMS found that ginkgo was efficient effective at reducing the severity of symptoms [90].

Precautions

No documentation

Side effects

The most typical side effects are GI distress and headache. These are present in fewer than 0.5 percent of the people in studies [91]. Cases of subdural hematoma have been reported due to ginkgo use [92].

Dosage

No documentation

Poisonous Management

No documentation

Line drawing

No documentation

References

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