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PubMed2005

Ginkgo biloba: persistent bleeding after total hip arthroplasty caused by herbal self-medication.

We describe a case of persistent postoperative bleeding following total hip arthroplasty in which, initially, no obvious cause was identified. The patient was taking ginkgo biloba extract, an unlicensed herbal medicine taken to improve mental alertness. Ginkgo biloba is an anticoagulant that inhibits platelet-activating factor and is contraindicated with aspirin. Four weeks' postoperatively, the ginkgo was stopped, and the bleeding stopped 6 weeks later.

Aged↗
PubMed2005

Ginkgolides induce apoptosis and decrease cell numbers in mouse blastocysts.

In this report, we examine the cytotoxic effect of ginkgolides, the major components of Ginkgo biloba extracts, on the blastocyst stage of mouse embryos and on subsequent early postimplantation embryonic development in vitro. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay revealed that blastocysts treated with 5 or 10muM ginkgolide A or ginkgolide B showed increased apoptosis versus untreated controls. This could be correlated with the observation that ginkgolide-treated blastocysts showed a significant reduction in the average number of total cells in the blastocyst and trophectoderm/inner cell mass lineage versus controls. In addition, ginkgolide-pretreated blastocysts showed normal levels of implantation on culture dishes in vitro, but significantly fewer embryos reached the later stages of embryonic development in the treatment groups versus the controls, instead dying at relatively early stages of development. Our results collectively indicate that ginkgolide treatment of mouse blastocysts induces apoptosis, decreases cell numbers, retards early postimplantation blastocyst development, and increases early-stage blastocyst death. These novel findings provide important new insights into the effect of Ginkgo biloba extracts on mouse blastocysts.

Animals↗
PubMedDate not supplied

Protection by bilobalide of the ischaemia-induced alterations of the mitochondrial respiratory activity.

Ischaemia is a common feature of most vascular diseases. There is evidence from experimental and clinical studies that Ginkgo biloba extract protects tissues from ischaemia/reperfusion damages. Bilobalide seems to be responsible, at least in part, for this activity. However, the mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated during liver and brain ischaemia, since mitochondria alteration is an early event in ischaemia-induced damage. Bilobalide could prevent the decrease in respiratory activity induced by ischaemia in liver and in brain, both when glutamate/malate or succinate was used as substrate. Ischaemia decreased state 3 respiration rate and bilobalide prevented this decrease. While bilobalide was not able to prevent the decrease in adenine translocase activity, it protected complex I activity. Bilobalide allows mitochondria to maintain their respiratory activity in ischaemic conditions by protecting complex I and probably complex III activities. Hence, the energetic pool of tissues is preserved during the ischaemic period as well as its viability. This mechanism provides, a possible explanation for the anti-ischaemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.

Animals↗
PubMed1999

Protection of mitochondrial respiration activity by bilobalide.

Mitochondria alteration is an early event in ischemia-induced damage, and its prevention improves tissue survival upon reperfusion. Adenine translocase and complex I activities are rapidly affected by ischemia. Ginkgo biloba extract demonstrates anti-ischemic properties attributable to the terpenoid fraction, mainly due to the presence of bilobalide. The mechanism of the protection afforded by bilobalide is not yet known. In this work, the effects of bilobalide on mitochondrial respiration were investigated. Mitochondria isolated from rats treated with bilobalide (2 to 8 mg/kg) showed a dose-dependent increase in the respiratory control ratio, due to a lower oxygen consumption during state 4. Bilobalide also decreased the sensitivity of oxygen consumption to inhibition of complex I by Amytal or to inhibition of complex III by antimycin A or myxothiazol. There was no protection of complexes IV and V. It also increased the activity of complex I but not of adenine translocase. Similar effects were also obtained in vitro when control mitochondria were preincubated for 1 hr with 0.8 microg/mL bilobalide. Treatment of the rats with 8 mg/kg bilobalide also prevented the ischemia-induced decrease in state 3 of the mitochondrial respiration and thus the decrease in RCR. The protective effect of bilobalide on cellular ATP content observed under ischemic conditions can be correlated with the above observations. By protecting complex I and III activities, bilobalide allows mitochondria to maintain their respiratory activity under ischemic conditions as long as some oxygen is present, thus delaying the onset of ischemia-induced damage. This mechanism provides a possible explanation for the anti-ischemic properties of bilobalide and of Ginkgo biloba extract in therapeutic interventions.

Animals↗
PubMed2006

Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B.

Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In this study, we have examined the effects of herbal extracts used in dietary supplements on the function of organic anion-transporting polypeptide B (OATP-B; OATP2B1), which is expressed on human intestinal epithelial cells and is considered to be involved in the intestinal absorption of various drugs. Specifically, the effects of 15 herbal extracts on uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels considered likely to be attainable in the human intestine, extracts of bilberry, echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%, respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was concentration-dependent (IC(50) = 11.2 +/- 3.3 microg/ml) and reversible. Moreover, flavonol glycosides and catechins significantly inhibited the function of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP-B may be primarily attributable to flavonoids. The extracts of mulberry, black cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3-sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered substrates of OATP-B.

Camellia sinensis↗
PubMed2002

[The protective effect of EGb 761 in isolated isochemical/reperfused rat hearts].

This study was conducted to evaluate the effect of Ginkgo biloba extract (EGb 761) on the nitric oxide (NO) production in relation to the recovery of postischemic cardiac function in isolated working rat hearts. Rats were orally treated with various doses (25, 50, 75, and 100 mg/kg/day) of EGb 761 for 10 days. Hearts were isolated in "working mode" and subjected to 30 min ischemia followed by 120 min reperfusion. In the initial phase of reperfusion, NO production measured by electron spin resonance spectroscopy (ESR) was reduced by 85% in the 75 mg/kg/day of EGb 761 treated group in comparison with the drug-free ischemic/reperfused hearts. Inducible NO synthase (iNOS) messenger RNA (mRNA) measured by reverse transcription-polymerase chain reaction (RT-PCR) also was reduced by 41 and 58% in the groups treated with 75 and 100 mg/kg/day of EGb 761. Our findings show that EGb 761 directly acts as an NO scavenger and concomitantly inhibits the expression of iNOS mRNA. Thus, EGb 761 may act as a potent inhibitor of NO production under the condition of ischemia/reperfusion, improving the recovery of postischemic cardiac function.

Animals↗
PubMedDate not supplied

A review of antioxidants and Alzheimer's disease.

BACKGROUND: In this article, we review a diverse body of research and draw conclusions about the usefulness, or lack there-of, of specific antioxidants in the prevention of Alzheimer's disease (AD). METHODS: The National Library of Medicine's database was searched for the years 1996-2004 using the search terms "Alzheimer's, anti-oxidants, antioxidants." RESULTS: Over 300 articles were identified and 187 articles were selected for inclusion based on relevance to the topic. Agents that show promise in helping prevent AD include: 1) aged garlic extract, 2) curcumin, 3) melatonin, 4) resveratrol, 5) Ginkgo biloba extract, 6) green tea, 7) vitamin C and 8) vitamin E. CONCLUSIONS: While the clinical value of antioxidants for the prevention of AD is often ambiguous, some can be recommended based upon: 1) epidemiological evidence, 2) known benefits for prevention of other maladies, and 3) benign nature of the substance. Long-term, prospective studies are recommended.

Acetylcarnitine↗
PubMed1993

The effects of oxygenated free radicals on VEP spectral components in experimental diabetes.

In this experimental research, 33 Swiss albino rats were studied. They were divided into three equal groups as control, alloxan-diabetic (diabetic group) and alloxan-diabetic rats treated with ginkgo biloba extract (diabetic-GbE group). After two months of diabetes and before ophthalmoscopically visible diabetic retinopathy, flash VEPs of three groups were recorded and spectral analysis of VEPs was computed by Fast Fourier Transform (FFT) algorithm. Comparing the results of diabetic and diabetic-GbE groups with control group, we observed a significant increase in the amplitude (dB) of 5 Hz frequency for the left and right responses of rats. At some frequencies, we also found important differences between diabetic-GbE and control groups.

Animals↗
PubMed2005

[Clinical observation of Gingko biloba extract injection in treating early diabetic nephropathy].

OBJECTIVE: To observe the effect of Ginkgo biloba extract injection (GB) in treating early diabetic nephropathy (DN). METHODS: Sixty DN patients were divided into two groups, the treated group were treated by GB and Western medicine, and the control group were given Western medicine alone. The study lasted for 4 weeks. Fasting plasma glucose (FPG), blood pressure, 24 h urinary albumin excretion (UAE), endogenous creatinine clearance rate (Ccr), blood lipids and hemorheology indices were examined before and after the study. RESULTS: Compared with the control group, UAE were significantly decreased (P < 0.01); Ccr, blood lipids and hemorheology indices were all improved after treatment in the treated group (P < 0.05 or P < 0.01). But in FPG and blood pressure there was no significant change between the treated group and the control group (P > 0.05). CONCLUSION: GB is effective in treating early DN through decreasing urinary albumin excretion rate, regulating blood lipids, improving renal function and hemorheology.

Aged↗
PubMed2003

Investigation of the free radical scavenging activity of Ginkgo biloba L. leaves.

The free radical scavenging activity of methanolic, ethanolic and aqueous extracts from Ginkgo biloba leaves, has been determined by EPR (electron paramagnetic resonance) using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. The investigation has also included selected constituents of G. biloba leaves, protocatechuic and p-coumaric acids, quercetin, rutin, isoginkgetin and (+)-catechin.

Biphenyl Compounds↗
PubMed1982

Effects of Ginkgo biloba on arterial smooth muscle responses to vasoactive stimuli.

1. An extract of Ginkgo biloba (Gb), at a concentration (100 microgram/ml) that did not provoke isometrically-recorded contractions of rabbit aorta, was tested on the contractile effects of norepinephrine (NE), serotonin (5-HT) and dopamine (DA). 2. Gb potentiated the contractile effect of NE (reduced the EC50 from 75 to 36 nM), but had no obvious action on the contractile effects of 5-HT or DA. 3. These results indicate that low concentrations of Gb might influence catecholaminergic systems by an indirect mechanism.

Animals↗
PubMed1992

[Protection from uv-light-induced oxidative stress by nutritional radical scavengers].

Two series of examinations were carried out in two voluntary test groups for the purpose of elucidating the correlation between ultraviolet light load and oxidative stress as well as the way it is influenced by nutritive radical scavengers. After a 6 to 7-hour impact of sunshine on the whole body (sunbathing beach) at n = 8 a continuous progredient increase of thiobarbituric acid reactive substances could be identified in the serum (from 5.56 +/- 0.98 to 8.91 +/- 0.99 mumol/l, p < 0.001), which after new exposure to sunshine reached 11.3 +/- 2.4 mumol/l. Likewise, a 15-minute exposure to ultraviolet light at n = 24 induced increases of TBRS concentrations lasting from 1-2 days. After 14-day supplementation with beta-carotene (n = 6), D-alpha-tocopherol (n = 6), selenium (n = 6), and ginkgo biloba extract (n = 6) the extent of the oxidative stress could be inhibited during a second exposure to ultraviolet light up to the following efficiency: Se > Ginkgo > beta-carotene > vitamin E. The clastogenous effect of sunshine and ultraviolet light must be regarded as a factor for initiating and promoting cancerogenesis in the total organism. Concerning the aetiopathogenesis of malignant melanoma the paramagnetic properties of free radicals with their nonenergetic effects of the magnetic field have to be considered more carefully in scientific examinations.

Adult↗
PubMed2003

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.

Animals↗
PubMed1993

EGb 761 inhibits stress-induced polydipsia in rats.

The effect of daily treatments with Ginkgo biloba extract (EGb 761, IPSEN, France) on body weight and water intake of rats was followed for 15 days. During this period, two groups of rats, under slight ether anesthesia, were intubated and fed either EGb 761 (100 mg/kg b.wt. in 5% ethanol) or, for sham controls, 5% ethanol alone (6.6 ml/kg b.wt.). The increase in body weight was similar for the control and experimental groups. However, during the same period of time, the water intake, ml water/g b.wt./24 h, increased 37% in the controls. In EGb 761-treated rats, water intake remained unchanged. This suggests that EGb 761 treatment inhibits the development of polydipsia due to the stress of daily handling and intubation.

Animals↗
PubMed1998

Effect of Ginkor Fort on hypoxia-induced neutrophil adherence to human saphenous vein endothelium.

This study was performed to evaluate the effects of Ginkor Fort, a venotropic drug composed of Ginkgo biloba extract, troxerutine, and heptaminol, on neutrophil adherence to the endothelium of saphenous veins. When saphenous veins were incubated 2 h in hypoxic conditions, they showed a five- to sixfold increase in neutrophil adherence to the endothelium. Ginkor Fort at 0.3 mg/ml was able to inhibit this increase by 69%. These results were confirmed by observations in scanning electron microscopy. Ginkor Fort also inhibited the subsequent activation of these neutrophils, as evidenced by the inhibition of superoxide anion release. The biochemical mechanism of this inhibition of neutrophil adherence was studied on endothelial cells in culture. We observed that Ginkor Fort was able to inhibit the different steps of the activation of endothelial cells by hypoxia: the activation of phospholipase A2 and the decrease in adenosine triphosphate (ATP) content. By preventing the first step of the activation cascade, the decrease in ATP content, Ginkor Fort blocks the subsequent increase in neutrophil adherence as well as neutrophil activation. The biochemical mechanism evidenced in this work might explain the beneficial effect of this drug in the treatment of patients with chronic venous insufficiency.

Cell Adhesion↗
PubMed2006

Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets.

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A large body of evidence indicates that oxidative stress is involved in the pathophysiology of these diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. Thus antioxidants have been studied for their effectiveness in reducing these deleterious effects and neuronal death in many in vitro and in vivo studies. Increasing number of studies demonstrated the efficacy of polyphenolic antioxidants from fruits and vegetables to reduce or to block neuronal death occurring in the pathophysiology of these disorders. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these phenolic compounds. We will review some of these mechanisms and particular emphasis will be given to polyphenolic compounds from green tea, the Ginkgo biloba extract EGb 761, blueberries extracts, wine components and curcumin.

Alzheimer Disease↗
PubMed1997

Neuron degeneration induced by verapamil and attenuated by EGb761.

Calcium channel blockers are used as neuroprotective agents, as glutamate antagonists. However, it has been found that calcium channel blockers may compromise neuronal survival after long-term exposure. To explore the mechanisms of the toxicity of calcium channel blockers on neurons, we studied the morphological characteristics and biochemical changes of cultured cortical neurons treated with verapamil, a calcium channel blocker. We now report that cerebral cortical cultures exposed to verapamil for 48 h undergo neuronal degeneration in both concentration-dependent and time-dependent fashion, possibly partially through the activation of apoptosis. On the other hand, it was found that Ginkgo biloba extract (EGb761) attenuated verapamil-induced neuronal injury, suggesting the possibility of using verapamil combined with EGb761 clinically. Furthermore, both B-50 immunoactivity (BIA) and the concentration of intracellular calcium in single neurons ([Ca2+]i) decreased after a 48-h exposure to verapamil, suggesting that the mechanisms of verapamil-induced degeneration may be associated with the disruption of intracellular calcium homeostasis and the inhibition of normal axonal elongation.

Animals↗