Extract of Ginkgo biloba leaves reverses yohimbine-induced spatial working memory deficit in rats

Extract of Ginkgo biloba is used to alleviate age-related decline in cognitive function, which may be associated with the loss of catecholamines in the prefrontal cortex. The purpose of this study was to verify whether alpha-2 adrenergic activity is involved in the facilitative effects of extract of Ginkgo biloba on prefrontal cognitive function. Male Wistar rats were trained to reach criterion in the delayed alternation task (0, 25, and 50-s delay intervals). A pilot study found that 3 or 4 mg/kg of yohimbine (intraperitoneal) reduced the choice accuracy of the delayed alternation task in a dose and delay-dependent manner, without influencing motor ability or perseverative behaviour. Acute oral pre-treatment with doses of 50, 100, or 200 mg/kg (but not 25 mg/kg) of extract of Ginkgo biloba prevented the reduction in choice accuracy induced by 4 mg/kg yohimbine. These data suggest that the prefrontal cognition-enhancing effects of extract of Ginkgo biloba are related to its actions on alpha-2-adrenoceptors.

Effects of ginkgo biloba extract on cation currents in rat ventricular myocytes

Ginkgo biloba extract (GBE), a valuable natural product for cerebral and cardiovascular diseases, is mainly composed of two classes of constituents: terpene lactones (e.g., ginkgolide A and B, bilobalide) and flavone glycosides (e.g., quercetin and kaempferol). Its electrophysiological action in heart is yet unclear. In the present study, using whole-cell patch clamp technique, we investigated electrophysiological effects of GBE on cation channel currents in ventricular myocytes isolated from rat hearts. We found that GBE 0.01-0.1% inhibited significantly the sodium current (I-Na), L-type calcium current (I-Ca) and transient outward potassium current (IKto) in a concentration-dependent manner. Surprisingly, its main ingredients, ginkgolide A (GB A), ginkgolide B (GB B) and bilobalide (GB BA) at 0.1 mM did not exhibit any significant effect on these cation channel currents. These results suggested that GBE is a potent non-selective cation channel modulator in cardiaomyocytes. Other constituents (rather than GB A, GB B and GB BA) might be responsible for the observed inhibitory effects of GBE on cation channels. (C) 2004 Elsevier Inc. All rights reserved.

Adulteration and Poor Quality of Ginkgo biloba Supplements

Adulteration of Ginkgo products sold as unregistered supplements within the very large market of Ginkgo products (reputedly £650 million annually) through the post-extraction addition of cheaper (e.g. buckwheat derived) rutin is suspected to allow sub-standard products to appear satisfactory to third parties, e.g. secondary buyers along the value chain or any regulatory authorities. This study was therefore carried out to identify products that did not conform to their label specification and may have been actively adulterated to enable access to the global markets. 500 MHz Bruker NMR spectroscopy instrumentation combined with Topspin version 3.2 and a CAMAG HPTLC system (HPTLC Association for the analysis of Ginkgo biloba leaf) were used to generate NMR spectra (focusing on the 6–8 ppm region for analysis) and chromatograms, respectively. Out of the 35 samples of Ginkgo biloba analysed, 33 were found to contain elevated levels of rutin and/or quercetin, or low levels of Ginkgo metabolites when compared with the reference samples. Samples with disproportional levels of rutin or quercetin compared with other gingko metabolites are likely to be adulterated, either by accident or intentionally, and those samples with low or non-existent gingko metabolite content may have been produced using poor extraction techniques. Only two of the investigated samples were found to match with the High-Performance Thin-Layer Chromatography (HPTLC) fingerprint of the selected reference material. All others deviated significantly. One product contained a 5-hydroxytryptophan derivative, which is not a natural constituent of Ginkgo biloba. Overall, these examples either suggest a poor extraction technique or deliberate adulteration along the value chain. Investigating the ratio of different flavonoids e.g. quercetin and kaempferol using NMR spectroscopy and HPTLC will provide further evidence as to the degree and kind of adulteration of Gingko supplements. From a consumer perspective the equivalence in identity and overall quality of the products needs to be guaranteed for supplements too and not only for products produced according to a quality standard or pharmacopoeial monograph.

Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability

EGb 761 is a standardized extract from the Ginkgo biloba leaf and is purported to improve age-related memory impairment. The acute and chronic effect of EGb 761 on synaptic transmission and plasticity in hippocampal slices from young adult (8-12 weeks) and aged (18-24 months) C57B1/6 mice was tested because hippocampal plasticity is believed to be a key component of memory. Acutely applied EGb 761 significantly increased neuronal excitability in slices from aged mice by reducing the population spike threshold and increased the early phase of long-term potentiation, though there was no effect in slices from young adults. In chronically treated mice fed for 30 days with an EGb 761-supplemented diet, EGb 761 significantly increased the population spike threshold and long-term potentiation in slices from aged animals, but had no effect on slices from young adults. The rapid effects of EGb 761 on plasticity indicate a direct interaction with the glutamatergic system and raise interesting implications with respect to a mechanism explaining its effect on cognitive enhancement in human subjects experiencing dementia. (C) 2003 Elsevier Inc. All rights reserved.

Effect of Ginkgo biloba (EGb 761®) on differential gene expression

Supplementation of diets with plant extracts such as ginkgo biloba extract (EGb 761®) (definition see editorial) for health and prevention of degenerative diseases is popular. However, it is often difficult to analyse the biological activities of plant extracts due to their complex nature and the possible synergistic and/or antagonistic effects of their components. Genome-wide expression monitoring with high-density oligonucleotide arrays provides one way to examine the molecular targets of plant extracts and may prove a useful tool in evaluating their therapeutic claims. Here, we will briefly describe some of our work on the effect of EGb 761® on differential gene expression in relation to its potential anti-carcinogenic, photoprotective and neuromodulatory properties.

Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers

Acute doses of Ginkgo biloba have been shown to improve attention and memory in young, healthy participants, but there has been a lack of investigation into possible effects on executive function. In addition, only one study has investigated the effects of chronic treatment in young volunteers. This study was conducted to compare the effects of ginkgo after acute and chronic treatment on tests of attention, memory and executive function in healthy university students. Using a placebo-controlled double-blind design, in experiment 1, 52 students were randomly allocated to receive a single dose of ginkgo (120 mg, n=26) or placebo (n=26), and were tested 4h later. In experiment 2, 40 students were randomly allocated to receive ginkgo (120 mg/day; n=20) or placebo (n=20) for a 6-week period and were tested at baseline and after 6 weeks of treatment. In both experiments, participants underwent tests of sustained attention, episodic and working memory, mental flexibility and planning, and completed mood rating scales. The acute dose of ginkgo significantly improved performance on the sustained-attention task and pattern-recognition memory task; however, there were no effects on working memory, planning, mental flexibility or mood. After 6 weeks of treatment, there were no significant effects of ginkgo on mood or any of the cognitive tests. In line with the literature, after acute administration ginkgo improved performance in tests of attention and memory. However, there were no effects after 6 weeks, suggesting that tolerance develops to the effects in young, healthy participants.

Levantamento do perfil medicamentoso e frequência de associações entre o Ginkgo (Ginkgo biloba L.) e ácido acetilsalicílico, em usuários atendidos pela FarmaUSCS de São Caetano do Sul

O presente estudo teve por objetivo, verificar o perfil medicamentoso bem como a freqüência de associação entre Gingko biloba e ácido acetilsalicílico (AAS) em indivíduos atendidos pela Farmácia Escola da Universidade Municipal de São Caetano do Sul (USCS). Verificou-se através dos resultados obtidos que 62,75% dos usuários são do sexo feminino, estão entre 60 e 70 anos de idade, com indicação do uso deste fitoterápico para circulação, fazendo uso há mais de três meses e administrando diariamente a dose de 80mg. Dos entrevistados, 13,73% fazem associação deste fitoterápico com AAS, desconhecendo os riscos das possíveis interações entre estes dois medicamentos, pois o uso concomitante de Ginkgo e AAS, por aumentar a inibição da agregação plaquetária, pode ocasionar hemorragias.

Enraizamento de estacas de Ginkgo biloba tratadas com ácido indolbutírico e ácido bórico

Objetivou-se neste trabalho estudar o efeito do ácido indolbutírico (AIB) e do ácido bórico (B) no enraizamento de estacas de Ginkgo biloba. em estacas com duas folhas, medindo 15 cm de comprimento foram provocadas duas lesões na base de aproximadamente 2 cm, expondo o câmbio e procedeu-se à imersão por 10 segundos no tratamento correspondente, AIB (0, 1000, 2000 e 3000 mg L-1) na ausência ou presença de B (0 e 150 mg L-1). em seguida foram colocadas para enraizar em bandejas de polipropileno contendo areia lavada. O delineamento foi em blocos casualizados num fatorial 4X2, com seis repetições. Foram avaliadas porcentagem de estacas enraizadas, estacas não enraizadas e mortas, diâmetro e comprimento das raízes, aos 70 dias do tratamento. Os dados foram submetidos à análise de variância sendo previamente testados para normalidade pelo Teste de Shapiro-Wilk. As médias foram comparadas pelo Teste de Tukey. Os tratamentos com 2000 mg L-1 de AIB foram superiores à ausência de AIB (80,55% vs. 55,56%, respectivamente), não diferindo dos demais tratamentos. A utilização de B não afetou a taxa de enraizamento, de estacas não enraizadas e mortas, não havendo interação entre a concentração de AIB e a utilização ou não de B. O diâmetro e o comprimento das raízes não foram afetados pela utilização de AIB e B.

Estudo comparativo dos efeitos do extrato de Ginkgo biloba L. e Panax ginseng C.A. Meyer na reprodução de ratos machos e fêmeas Wistar

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo da ação do extrato de Ginkgo biloba e amido hidroxietílico hipertônico na atenuação de alterações decorrentes de isquemia e reperfusão de órgãos esplâncnicos em ratos

A oclusão e reperfusão das artérias esplâncnicas ocasiona choque circulatório, causado principalmente pelo aumento de permeabilidade vascular e pela agressão celular provocada por radicais livres derivados do oxigênio. Este estudo tem por finalidade verificar a ação do extrato de Ginkgo biloba (Egb-761) e do amido hidroxietílico (AHH) na prevenção do choque circulatório produzido pela isquemia e reperfusão de órgãos esplâncnicos. O Egb-761 tem propriedades antioxidantes relatadas na literatura. O AHH, tem sido utilizado como recurso terapêutico do choque hipovolêmico. Ratos anestesiados receberam infusão contínua de Egb-761 ou AHH, sendo submetidos à isquemia (oclusão do tronco celíaco, artéria mesentérica superior e artéria mesentérica inferior por 30 minutos) e reperfusão (por 90 minutos) dos órgãos esplâncnicos. Foram feitas: análise histopatológica ileal, dosagem de malondialdeído ileal e determinação contínua da pressão arterial média (PAM). A PAM ao final do período de reperfusão foi significativamente mais elevada nos animais tratados com Egb-761 e AHH, que no grupo controle (F=18,29; p<0,001). Não houve diferença entre os grupos tratados e controle quanto à dosagem de MDA (H=4,61; p>0,10) e quanto às alterações histológicas (H=6,003; p>0,10). em conclusão, houve melhora nas condições hemodinâmicas, com atenuação do choque nos ratos que receberam Egb-761 ou AHH. Novos estudos serão necessários para se avaliar melhor as alterações histológicas e para esclarecer a formação de produtos finais da peroxidação lipídica.

Effect of Ginkgo biloba on the reproductive outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats

The aim of the present study was to evaluate the effect of Ginkgo biloba treatment (EGb 761, 200 mg kg-1 day-1) administered from day 0 to 20 of pregnancy on maternal reproductive performance and on the maternal and fetal liver antioxidant systems of streptozotocin-induced diabetic Wistar rats. on day 21 of pregnancy, the adult rats (weighing approximately 250 ± 50 g, minimum number = 13/group) were anesthetized to obtain maternal and fetal liver samples for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total glutathione (GSH-t) determinations. The uterus was weighed with its contents. The diabetic (G3) and treated diabetic (G4) groups of rats presented significant maternal hyperglycemia, reduced term pregnancy rate, impaired maternal reproductive outcome and fetal-placental development, decreased GSH-Px (G3 = G4 = 0.6 ± 0.2) and SOD (G3 = 223.0 ± 84.7; G4 = 146.1 ± 40.8), and decreased fetal CAT activity (G3 = 22.4 ± 10.6; G4 = 34.4 ± 14.1) and GSH-t (G3 = G4 = 0.3 ± 0.2), compared to the non-diabetic groups (G1, untreated control; G2, treated). For G1, maternal GSH-Px = 0.9 ± 0.2 and SOD = 274.1 ± 80.3; fetal CAT = 92.6 ± 82.7 and GSH-t = 0.6 ± 0.5. For G2, G. biloba treatment caused no toxicity and did not modify maternal or fetal-placental data. EGb 761 at the nontoxic dose used (200 mg kg-1 day-1), failed to modify the diabetes-associated increase in maternal glycemia, decrease in pregnancy rate, decrease in antioxidant enzymes, and impaired fetal development when the rats were treated throughout pregnancy (21 days).

Protective effects of Ginkgo biloba against rat liver carcinogenesis

Ginkgo biloba (EGb) has been proposed as a promising candidate for cancer chemoprevention and has shown protective effects on the liver against chemically induced oxidative injury and fibrosis. The potential beneficial effects of EGb were investigated in two rat liver carcinogenesis bioassays induced by diethylnitrosamine (DEN). In a short-term study for anti-initiating screening, male Wistar rats were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb and initiated 14 days later with a single dose of DEN (100 mg/kg i.p.). The respective groups were killed 24 h or 2 weeks after DEN-initiation. Liver samples were collected for the analysis of proliferating cell nuclear antigen (PCNA), transforming growth factor alpha (TGF-alpha), p53, apoptosis and induction of single hepatocytes and minifoci positive for the enzyme glutathione S-transferase P-form (GST-P). In a medium-term study for anti-promoting screening, the animals received a single dose of DEN (200 mg/kg i.p.) and, 2 weeks later, were fed a basal diet or supplemented diet with 500 or 1000 ppm EGb for 6 weeks. All animals underwent 70% partial hepatectomy (PH) at week 3 and killed at week 8. Liver samples were colleted to analyze development of preneoplastic foci of altered hepatocytes (FAH) expressing GST-P. In the short-term study, pretreatment of rats with 1000 ppm EGb significantly reduced the rates of cell proliferation, apoptosis and p53, TGF-a immunoreactivity and the number of GST-P-positive hepatocytes. In the medium-term study, EGb treatment during the post-initiation stage failed to reduce the development of DEN-induced GST-P-positive foci. Thus, EGb presented inhibitory actions during initiation but not promotion of rat liver carcinogenesis induced by DEN. (C) 2008 Elsevier B.V. All rights reserved.

Estudo do extrato de Ginkgo biloba na prevenção de malformações em recémnascidos de ratas diabéticas

The pregnant women presenting Diabetes mellitus develop metabolic alterations, that may cause damage to the fetal well-being and provoke anomalies and/or malformations. The antioxidant treatment has improved the embryonic development from streptozotocin diabetic rats. Several studies have shown that a Gingko biloba extract presents antioxidant effects and, in the present study, one of the G. biloba extract formulations was used (EGb761) - Tebonin (200 mg/Kg/day), given to the diabetic pregnant female rats. The aim was to evaluate the effect of the EGb761 treatment on the of anomalies and/ or malformations incidence of the offspring. Diabetes was induced in female rats using streptozotocin in a dose of 40 mg/kg. The rats were mated, and the pregnant animals were divided in two groups: Control (water) and experimental (G. biloba). At day 21 of pregnancy, the rats were killed, and their fetuses were analyzed and processed for anomalies and/or malformations incidence. The results demonstrated that control and experimental groups presented no external anomalies and malformations; increased incidence of skeletal anomalies and of visceral malformations, and lower rate of visceral anomalies and skeletal malformations. These data confirm no statistical difference and, therefore, EGb761 treatment did not cause changes. Thus, a dose of 200 mg/Kg/day of a Gingko biloba extract given during the pregnancy rat was ineffective in the prevention of the anomalies and/or malformations related to the diabetes.