Life Extension - Treatment using Supplements

Ginkgo Biloba - updated: 23 February 2009

Ginkgo biloba and neurodegenerative disorders

Front Biosci. 2004 Sep 1;9:3091-104

Christen Y.

The Gingko biloba extract EGb 761 has been the subject of many studies which confirm its usefulness for the prevention and treatment of neurodegenerative pathologies. These studies have focused on: a) the probable mechanisms of action that are involved in these disorders (including non-specific mechanisms implicated in diverse neurodegenerative disorders, particularly oxidative stress, or specific mechanisms such as those associated with beta-amyloid in Alzheimer's disease) and the processes of neuronal death; b) available animal models, and c) healthy individuals or those suffering from mild cognitive impairment or Alzheimer's disease. This data must be completed, particularly with regard to new knowledge about the pathogenesis of these disorders. Ambitious interventional studies are underway and may provide new evidence regarding the effect of EGb 761 in preventing Alzheimer's disease in humans. Positive findings would be particularly interesting since this drug is very safe to use.

Publication Types:

• Review

Alzheimer's disease, the nematode Caenorhabditis elegans, and ginkgo biloba leaf extract

Life Sci. 2006 Mar 27;78(18):2066-72

Luo Y.

Alzheimer's disease (AD) is affecting larger and larger proportions of our population as lifespan increases. Thus, the means to prevent or reduce the rate of this disorder is a high priority for medical research. A standardized extract of Ginkgo biloba leaves EGb 761 is a popular dietary supplement taken by the general public to enhance mental focus and by the elderly to delay onset of age-related loss of cognitive function. EGb 761 has been used for treatment of certain cerebral dysfunctions and dementias associated with aging and AD. Substantial evidence indicates that EGb 761 has neuroprotective effects. But, mechanisms of action of the components of the extract are, unfortunately, poorly understood. Research in my laboratory focuses on understanding mechanisms of action of the components of the herbal extract EGb 761 in protection against Alzheimer's disease. We have demonstrated that EGb 761 inhibited amyloid beta aggregation in vitro and attenuates reactive oxidative species (ROS) in a model organism - the round worm Caenorhabditis elegans. Furthermore, EGb 761 eased its toxicity in the transgenic C. elegans. We also found that only a certain size of the amyloid beta aggregates is toxic to the worms. These findings suggest that EGb 761 has a clear therapeutic potential for prevention and/or treatment of AD. A better understanding of the mechanisms of neuroprotection by EGb 761 will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine.

Publication Types:

• Review

Ginkgo biloba extract (EGb 761) in Alzheimer's disease: is there any evidence?

Curr Alzheimer Res. 2007 Jul;4(3):253-62

Ramassamy C, Longpré F, Christen Y.

For centuries, extracts from the leaves of the Ginkgo biloba tree have been used as Chinese herbal medicine to treat a variety of health disorders. The standardized Ginkgo biloba extract EGb 761 was marketed in France and Germany 30 years ago for various vascular and cerebral deficits and is now classified as a food supplement in the United States. EGb 761 is currently the focus of phase-III clinical trials, GEM and GuidAge studies, to evaluate its efficacy on the prevention of Alzheimer's disease (AD) in subjects over 70 years old. This review summarizes recent advancements in our understanding of the potential role of EGb 761 in the prevention of AD. Besides its well-known free radical scavenging properties, the ability of EGb 761 to protect neurons probably also involves other intracellular pathways. We will point out potential targets of EGb 761 in the amyloid cascade such as its antiamyloidogenic properties or the regulation of gene expression. Moreover we will discuss the complexity of the cellular and molecular mechanisms of EGb 761 and the significance of the synergic effect of different constituents of EGb 761.

Publication Types:

• Review

Ginkgo biloba--an appraisal

Kathmandu Univ Med J (KUMJ). 2004 Jul-Sep;2(3):225-9

Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY.

Ginkgo biloba has been used in traditional Chinese medicine for about 5000 years. A standardized preparation, EGb 761 has been recently prepared. The pharmacologically active constituents, flavonol glycosides and the terpene lactones are standardized. The terpene lactones comprise of ginkgolides A, B, C and bilobalides. The extract scavenges excess free radicals and pretreatment with EGb 761 reduces damage by free radicals in patients undergoing coronary bypass surgery. The action of platelet activating factor is antagonized and platelet aggregation is reduced. Blood flow is increased. Release of prostacyclines and nitric oxide was shown to be stimulated. Ginkgo biloba has been found to be useful in the treatment of Alzheimers disease and cognitive impairment. EGB 761 has shown beneficial effect in aging and mild cognitive impairment. Bilobalide has been shown to be protective against glutamate-induced excitotoxic neuronal death. Early studies indicate a potential role in age-related macular degeneration and some types of glaucoma. Anticancer action is related to antioxidant, anti-angiogenic and gene regulatory actions. Ginkgo biloba has shown overall improvement in about 65% of patients with cerebral impairment and a similar percentage suffering from peripheral vascular diseases. A recent study suggested that phytoestrogens in Ginkgo biloba may have a role as alternative hormone replacement therapy. Recent trials have not shown a beneficial effect of Ginkgo biloba in tinnitus and acute mountain sickness. Ginkgo biloba increased the bioavailability of diltiazem. The extract has been shown to protect against doxorubicin-induced cardiotoxicity and gentamicin-induced nephrotoxicity in animals. Ginkgo biloba inhibits microsomal enzymes and has a potential for drug interactions. Further studies to establish the efficacy of Ginkgo biloba are required.

Publication Types:

• Review

Pharmacological studies supporting the therapeutic use of Ginkgo biloba extract for Alzheimer's disease

Pharmacopsychiatry. 2003 Jun;36 Suppl 1:S8-14

Ahlemeyer B, Krieglstein J.

The standardized Ginkgo biloba extract EGb 761(definition see editorial) has been shown to produce neuroprotective effects in different in vivo and in vitro models. Since EGb 761 is a complex mixture containing flavonoid glycosides, terpene lactones (non-flavone fraction) and various other constituents, the question arises as to which of these compounds mediates the protective activity of EGb 761. Previous studies have demonstrated that the non-flavone fraction was responsible for the antihypoxic activity of EGb 761. Thus, we examined the neuroprotective and anti-apoptotic ability of the main constituents of the non-flavone fraction, the ginkgolides A, B, C, J and bilobalide. In focal cerebral ischemia models, the administration of bilobalide (5-20 mg/kg, s. c.) 60 min before ischemia dose-dependently reduced the infarct area in mouse brain and the infarct volume in rat brain 2 days after the onset of the injury. 30 minutes of pretreatment with ginkgolide A (50 mg/kg, s. c.) and ginkgolide B (100 mg/kg, s. c.) reduced the infarct area in the mouse model of focal ischemia. In primary cultures of hippocampal neurons and astrocytes from neonatal rats, ginkgolide B (1 microM) and bilobalide (10 microM) protected the neurons against damage caused by glutamate (1 mM, 1 h) as evaluated by trypan blue staining. In addition, bilobalide (0.1 microM) was able to increase the viability of cultured neurons from chick embryo telencepalon when exposed to cyanide (1 mM, 1h). Furthermore, we attempted to find out whether ginkgolides A, B, and J and bilobalide were also able to inhibit neuronal apoptosis (determined by nuclear staining with Hoechst 33 258 and TUNEL-staining). Ginkgolide B (10 microM), ginkgolide J (100 microM) and bilobalide (1 microM) reduced the apoptotic damage induced by serum deprivation (24h) or treatment with staurosporine (200 nM, 24h) in cultured chick embryonic neurons. Bilobalide (100 microM) rescued cultured rat hippocampal neurons from apoptosis caused by serum deprivation (24h), whereas ginkgolide B (100 microM) and bilobalide (100 microM) reduced apoptotic damage induced by staurosporine (300 nM, 24h). Ginkgolide A failed to affect apoptotic damage neither in serum-deprived nor in staurosporine-treated neurons. The results suggest that some of the constituents of the non-flavone fraction of EGb 761 possess neuroprotective and anti-apoptotic capacity, and that bilobalide is the most potent one. In contrast, ginkgolic acids (100-500 microM) induced neuronal death, which showed features of apoptosis as well as of necrosis, but these constituents were removed from EGb 761 below an amount of 0.0005 %. Taking together, there is experimental evidence for a neuroprotective effect of EGb 761 that agrees with clinical studies showing the efficacy of an oral treatment in patients with mild and moderate dementia.

Publication Types:

• Review

Ginkgo biloba extract EGb 761 protects against mitochondrial aging in the brain and in the liver

Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):685-92

Sastre J, Lloret A, Borrás C, Pereda J, García-Sala D, Droy-Lefaix MT, Pallardó FV, Viña J.

According to the free radical theory of aging, oxygen-derived free radicals causes the age-associated impairment at the cellular and tissue levels. The mitochondrial theory of aging points to mitochondria, and specially mitochondrial DNA, as the major targets of free radical attack upon aging. Thus, oxidative damage to mtDNA accumulate with age in human and rodent tissues and also is inversely related to maximum life span of mammals. Mitochondrial deficits, such as a decrease in mitochondrial membrane potential, occur upon aging due to oxidative damage. The age-related mitochondrial oxidative stress may be prevented by late onset administration of certain antioxidants, such as Ginkgo biloba extract EGb 761. These antioxidants may also delay the physiological impairment associated with aging.

Publication Types:

• Review

Ginkgo biloba leaf extract: review of biological actions and clinical applications

Antioxid Redox Signal. 1999 Winter;1(4):469-80

Yoshikawa T, Naito Y, Kondo M.

The number of studies on Ginkgo biloba leaves is rapidly increasing. A variety of effects of Ginkgo biloba leaf extract (GBLE) have been identified. GBLE contains many different flavone glycosides and terpenoides. GBLE has an antioxidant action as a free radical scavenger, a relaxing effect on vascular walls, an antagonistic action on platelet-activating factor, an improving effect on blood flow or microcirculation, and a stimulating effect on neurotransmitters. Besides a direct scavenging action on active oxygen species, GBLE exerts an anti-inflammatory effect on inflammatory cells by suppressing the production of active oxygen and nitrogen species. GBLE inhibited the increase in the products of the oxidative decomposition low-density lipoprotein (LDL), reduced the cell death in various types of neuropathy, and prevented the oxidative damage to mitochondria, suggesting that GBLE exhibits beneficial effects on neuron degenerative diseases by preventing chronic oxidative damage. The study using a model of ischemia-reperfusion injury has also demonstrated the protective effect of GBLE on cardiac muscle and its antioxidative action in vivo. Favorable results have been obtained in double-blind, placebo-controlled, comparative trials of patients with memory disorders, obstructive arteriosclerosis, and dementia. We review the recent studies on GBLE with respect to its various pharmacological actions, such as a scavenging activity on free radicals and an inhibitory action on lipid peroxidation. GBLE shows a very strong scavenging action on free radicals, and is thus considered to be useful for the treatment of diseases related to the production of free radicals, such as ischemic heart disease, cerebral infarction, chronic inflammation, and aging.

Publication Types:

• Review

Publication Types:

• Review