Index
- Description of the plant: habitat and hints of botany
- Constituents of the drug and preparations
- Phytotherapeutic uses
- Drug interactions
- Side effects
- Conclusion
Questions and answers
Description of the plant: habitat and hints of botany
Ginkgo biloba L. (Fam. Ginkgoaceae) is a tree of Asian origin, up to 40 meters high and dioecious (with male and female sexual organs on distinct individuals). This plant is the only survivor of the Ginkgoales , an order originated according to phylogenetic studies in the Mesozoic era. In addition to being present on earth for more than 200 million years, ginkgo is an extremely long-lived plant, capable of reaching 1000 years of life and extremely resistant to environmental conditions, so much so that it deserves the nickname “tree of life”.
In Japan, ginkgo is considered sacred , while its presence in Europe began following imports for ornamental reasons, which took place around the 18th century.
The drug is made up of dried leaves, whose typical fan shape is easily recognizable and identifiable in many phytotherapy texts. The leaves, bilobed and petiolate , take on an intense yellow color in winter before detachment. The term “ginkgo” derives in fact from the Japanese Yin-kuo, literally “golden apricot” , recalling the suggestive autumnal aspect of the plant.
The seeds are sold as anthelmintics in eastern markets, however, although the inner part of the seeds is edible after roasting, the fleshy outer part, greenish-yellow in color, contains toxic substances such as ginkgotoxin , a neurotoxin capable of inducing epileptic seizures., as well as irritants capable of inducing severe dermatitis .
Constituents of the drug and preparations
Ginkgo biloba leaves contain several constituents among which terpenes and flavonoids stand out . Among the latter, there is a high quantity of flavone compounds, both dimeric flavones such as amentoflavone and bilobetin , and flavonols derived from kaempferol and quercetin . The highest flavonoid content is found in fresh leaves harvested in May .
Among the terpene derivatives we can include: sesquiterpenes (such as bilobalide), diterpenes (such as ginkgolides A, B, C, M and J) and other terpene compounds.
According to the European Pharmacopoeia X, the leaves must have a minimum content of 0.5% of flavonoids expressed as flavone glycosides, while the dry extract (derived from them) is defined by the ESCOP monographs according to the following composition parameters: 22-27% of flavonoids, 2 , 6-3.2% of bilobalide, 2.8-3.4% ginkgolides A, B and C. In the extract the content of ginkgolic acids, compounds with cytotoxic properties, must be less than 5 ppm.
Among the possible preparations from the leaves, the acetone extract (60%) is among the best known and studied, in fact there is a commercial formulation called EGb761® used in several clinical studies characterized by: 24% flavonic glycosides (quercetin, kaempferol and isoramnetina ) and 6% terpene lactones(ginkgolides A, B, C and bilobalide).
Generally dry extracts are administered orally, at a dose of 120-240 mg per day, in the form of tablets or capsules, to be taken in two different doses.
Phytotherapeutic uses
The medicinal use of ginkgo has a thousand-year tradition in various fields of application. The leaves are mainly used for the improvement of peripheral microcirculation , in particular in the cerebral field . The main biological activities supported by the scientific literature are described below.
Cognitive effects
Ginkgo extracts are used in the treatment of symptoms of cognitive impairment and in the early stages of Alzheimer’s disease . Indications for use include memory loss and other cognitive disorders in the elderly , including dizziness and headache . The EMA also reports the established use of ginkgo leaf extract to improve cognitive impairment, associated with both age and dementia.
The effects on memory , on learningand on recovery following brain damage, are documented by various researches in in vitro and animal models, in order to understand their mechanisms of action. Numerous studies have shown that ginkgo extracts have neuroprotective effects, improving vasodilation by releasing nitric oxide and inhibiting the angiotensin converting enzyme (ACE, responsible for the conversion of angiotensin I to angiotensin II).
The main bioactive compound of the extract appears to be ginkgolide B , a molecule capable of crossing the blood brain barrier, especially in conditions of ischemia , with documented anti-inflammatory activitytestified by the inhibition of the nuclear transcription factor NF-κB.
Treatment with EGb761® extract reduces amnesia in animal models by improving short-term memory. The activity of the extract is associated with the enhancement of cholinergic transmission , an activity that in the central nervous system is connected to mnemonic processes. Furthermore, ginkgo extracts promote neurogenesis by increasing the expression of neurotrophin (NGF), which also has a beneficial effect on neuron survival.
Some systematic reviews and numerous clinical studies have been conducted to evaluate the effectiveness of ginkgo in cognitive deficits, without however arousing unanimous consent from the scientific community.
A first systematic review in 2009 evaluated the effects of EGb761® in several clinical studies ; among the most recent studies, only one has shown actual improvement. A more recent systematic review, in 2016, concluded that ginkgo treatment has potential in treating cognitive deficits, but only at dosages above 200 mg and for periods longer than five months.
Finally, a recent review has confirmed that treatment with EGb761® improves the late symptoms of dyskinesia induced by treatment with antipsychotics , in patients with schizophrenia..
Anti-PAF activity
The ginkgolides , particularly ginkgolide B, are known receptor antagonists for the PAF (factor of platelet activation ) and cause the reduction in platelet aggregation, the degranulation of neutrophils and the production of oxygen radicals (ROS), acting also as a scavenger of radical species.
Furthermore, the activation of the PAF receptor induces apoptosis and the release of glutamate , a molecule that acts as a neurotoxic factor. In vitro studies have shown that ginkgo extracts improve mitochondrial dysfunction caused by ROS, decreasing the activity of caspases 3 and 12 and of apoptotic factors.
Among the other antagonistic effects found are also the reduction of bronchoconstriction , infiltration of inflammatory cells and hypotension induced by PAF. The data collected show the possible mechanism of action, but there are no confirmatory data on humans, therefore caution is required in their interpretation.
Circulatory disorders
According to the EMA, the traditional use of the pulverized drug of ginkgo reduces some phenomena related to circulation problems , such as heaviness in the legs and the sensation of cold in the extremities.
The ginkgo (leaves and buds) is included in Annex 1 (DM August 10, 2018) which lists the medicinal plants that can enter into the composition of food supplements, which is also reported its physiological use as “Normal blood circulation. Functionality of the microcirculation. ” The mechanism of action appears to be linked to inhibition of the ACE enzyme, reducing vasoconstriction and improving endothelial function.
Ginkgo in humans is also used to treatcirculatory problems , such as peripheral arteriopathies , and to improve the duration of walking in people with intermittent claudication , symptoms of Raynaud’s disease , acrocyanosis and postphlebitic syndrome .
Intermittent claudication is a disease that manifests itself with cramps and muscle pain , usually localized to the calf , often due to occlusive pathologies of peripheral arteries. A meta-analysis confirmed that the use of ginkgo is capable of increasing distancestraveled by patients before the onset of symptoms. The effects on Raynaud’s disease, characterized by vasospasms often visible on the extremities such as the fingers, are variable and not all studies report positive data, while a 2020 meta-analysis established that the use of ginkgo improves neurological function. of patients with ischemia, but does not improve quality of life or reduce the risk of other ischemic events.
Several studies have underlined how ginkgo extracts improve microcirculation , especially in elderly patients , by increasing viscoelasticity values.of the vessels both in the skin and in internal organs such as the liver. The effects were found through blood flow measurements and are confirmed by the increase in vasodilatory molecules (such as cAMP and cGMP). A 2018 systematic review showed that EGb761® extract improves the symptoms of tinnitus (or tinnitus), this disorder can arise from several causes, but one of the most common is inadequate blood supply to the inner ear.
Premenstrual syndrome and menopause
A systematic review identified two clinical studies on the use of ginkgo in the treatment of premenstrual syndrome . A first study highlighted how the use of ginkgo is limited to the reduction of mastalgia , while the second highlighted beneficial effects in various physical and psychological symptoms.
Other research has evaluated ginkgo’s ability to improve female sexual desire , with mixed results. However, two studies have shown positive effects on desire during menopause and in women with sexual dysfunction caused by antidepressants .
Eye disorders
Ginkgo has also been evaluated in relation to visual disturbances and visual field damage, such as glaucoma , age-related macular degeneration and diabetic retinopathy .
The previously mentioned circulatory effects have a potential useful mechanism in glaucoma, while in vitro ginkgolide B has shown an anti-apoptotic effect on retinal ganglion cells.
A review of the literature showed that the use of ginkgo to improve blood flowand visual performance in glaucoma patients is very limited. In addition, a review of the use of ginkgo in the treatment of macular degeneration has shown some beneficial effects , but the data are preliminary and further investigation is needed. Most of the findings supporting these conditions come from studies in animal models.
Drug interactions
Several studies have evaluated the effect of ginkgo extracts on cytochromes and P-glycoprotein . Although the results are variable, the potential drug interaction effect through modulation of these enzymes or transporters can generally be considered minor or negligible . Considering the effects on PAF, it is possible that ginkgo may increase the risk of bleeding in patients treated with anticoagulant or antiplatelet drugs , as found in some isolated and documented cases, but dedicated clinical studies have not yet highlighted this interaction in humans.
Despite this evidence, there are some clinical cases ofdrug interactions reported in the literature with the following drugs (class and side effect reported in parentheses): risperidone (antipsychotic, priapism), trazodone (antidepressant, coma), valproic acid and phenytoin (anticolvusants, fatal seizures) and efavirenz (antiviral, reduced efficacy ). The data supporting these interactions are still preliminary, but extreme caution must be exercised, under the strict supervision of the treating physician.
Side effects
Due to the progressive increase in the use of ginkgo , over the last decade the reports of adverse events have increased , such as: edema, fever, urticaria, anemia , angina pectoris, tinnitus, hepatitis , arthralgia, insomnia, dyspnoea and haemorrhage.
Among the undesirable effects of the drug, gastrointestinal disorders , headache , allergic reactions and haemorrhages were observed , the latter especially when used in combination with antiplatelet agents .
According to the Ministry of Health, ginkgo should not be taken if you are pregnant or breastfeedingFurthermore, it is strongly recommended to consult a doctor in case of concomitant anticoagulant therapy.
Conclusion
Ginkgo is a suggestive plant with an undoubted charm, both in the phytotherapeutic and historical fields . Fortunately, phytotherapy is linked to scientific evidence and does not contemplate myths and suggestions, except as possible areas of investigation.
The effects of this plant, or rather of its leaves , are well documented at the level of the nervous system , in particular in contexts of cognitive deficit , and at the circulatory level , in the improvement of peripheral arteriopathies . However, it is worth remembering that although it is often associated with memory improvement, dedicated studies have never shown beneficial effects in healthy subjects, but only in pathological areas.
Certainly interesting are the effects of ginkgo on the female reproductive system , deserving of further study in the future. The consumption of ginkgo is not free from side effects, even serious , it is therefore useful to evaluate the most appropriate therapy with the advice of your doctor .
MORE INFORMATION
- Book: Pharmacognosy and phytotherapy: pharmacological bases and application aspects.
Authors: Mazzanti G, Dell’Agli M, Izzo A.
Publisher: Piccin
Year: 2020 - Book: Phytotherapy: rational use of plant drugs
Authors: Capasso F, Grandolini G, Izzo A.
Publisher: Springer
Year: 2006 - Book: ESCOP Monographs 2nd edition
Authors: European Scientific Cooperative On Phytotherapy
Publisher: Thieme
Year: 2003
Questions and answers
CAN GINKGO BE A GOOD MEMORY AID?
Scientific data show that ginkgo improves conditions of cognitive impairment, especially related to senile dementia, but has no effect on the memory of a healthy subject. The effects appear to be related to dosages above 200 mg and treatment times of over 5 months.
DOES THE USE OF GINKGO STRENGTHEN THE BODY AND INCREASE LIFE EXPECTANCY?
There is no evidence that ginkgo affects longevity or endurance. Furthermore, treatment with ginkgo can lead to even serious side effects, partly linked to drug interactions, so its use should always be brought to the attention of your doctor.
CAN I TAKE GINKGO IF I AM PREGNANT OR BREASTFEEDING?
The use of ginkgo is not recommended in pregnant and lactating women, to date there are no studies that can guarantee the safety of the fetus or baby.
DO GINKGO SEEDS, SOMETIMES MISTAKENLY REFERRED TO AS “FRUITS”, HAVE HEALTH BENEFITS?
No, ginkgo seeds are an irritating and potentially toxic product. The fleshy part can cause severe allergic reactions, as well as cause food poisoning characterized by loss of consciousness.
