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PubMed2006

Ginkgo biloba: no robust effect on cognitive abilities or mood in healthy young or older adults.

Ginkgo biloba extracts are commonly used to prevent or treat memory problems but evidence on the efficacy of ginkgo is equivocal. In any case, the psychological locus of ginkgo's effects is unknown. A 12-week, double-blind, placebo-controlled study assessed effects of ginkgo (120 mg per day) on a wide range of cognitive abilities, executive function, attention and mood in 93 healthy older adults (55-79 years) and in 104 young adults (18-43 years). For the older adult sample, longer-term memory assessed by associational learning tasks showed improvement with ginkgo (d = 0.52, p = 0.04). There was no statistically significant difference on any other measure. For the young adult group no measure showed statistically significant effects of ginkgo enhancement. There were no side effects unequivocally attributable to treatment with ginkgo and those reported by participants in the ginkgo groups were mild and similar to those reported elsewhere.

Adolescent↗
PubMed2000

Cardioprotective effects of the calcineurin inhibitor FK506 and the PAF receptor antagonist and free radical scavenger, EGb 761, in isolated ischemic/reperfused rat hearts.

Effects of the calcineurin inhibitor FK506, the platelet-activating factor (PAF) antagonist, and free radical scavenger Ginkgo biloba extract, EGb 761, and their combination on reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), and recovery of cardiac function were studied after 30 min of global ischemia followed by 2 h of reperfusion in isolated rat hearts. In the first series of studies, rats received a daily (oral) dose of 0, 1, 5, 10, 20, or 40 mg/kg/day FK506 for 10 days. FK506 dose-dependently reduced the incidence of reperfusion-induced total (irreversible plus reversible) VF from a value of 92% for untreated animals to 92% (NS), 83% (NS), 67% (NS), 33% (p<0.05), and 25% (p<0.05), for doses of 1-40 mg/kg/day, respectively, with effects on incidence of VT showing the same pattern. FK506, between 20 and 40 mg/kg/day, also resulted in significant recovery of postischemic cardiac function. In the second series of studies, rats were treated with EGb 761 alone or in combination with FK506. Whereas no significant reduction in arrhythmias or improvement in cardiac function resulted from a single intervention of EGb 761 at 25 mg/kg/day, combined treatment of rats with 25 mg/kg/day of EGb 761 and 1 or 5 mg/kg/day of FK506 resulted in a reduction in total and irreversible VF of 92% and 92% to 42% (p<0.05) and 33% (p<0.05), 25% (p<0.05) and 8% (p<0.05), respectively, versus untreated control animals, paralleled by similar effects on the incidence of VT and accompanied by significant improvements in postischemic cardiac function. Our results demonstrate a novel cardioprotective characteristic of FK506 and suggest that combination therapy by using FK506 plus EGb 761 synergistically improves postischemic cardiac function, while reducing the incidence of reperfusion-induced VF and VT, which may expand the clinical utility of FK506 and allow therapy with FK506 at lower doses than are currently useful.

Animals↗
PubMed1999

The protective effect of EGb 761 in isolated ischemic/reperfused rat hearts: a link between cardiac function and nitric oxide production.

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 of reperfusion. EGb 761 inhibited NO production measured by electron spin-resonance spectroscopy (ESR), and improved the recovery of postischemic cardiac function (coronary flow, aortic flow, left ventricular developed pressure and its first derivative) in the ischemic/reperfused myocardium. Thus in rats treated with 25, 50, 75, and 100 mg/kg/day of EGb 761 and in hearts subjected to 30-min ischemia followed by 120 min of reperfusion, aortic flow was increased from its postischemic drug-free control value of 8.0+/-0.4 to 8.6+/-0.4 ml/min (NS), 17.3+/-0.9 ml/min (p<0.05), 21.5+/-1.1 ml/min (p<0.05), and 23.6+/-1.2 ml/min, respectively. The same recovery in postischemic coronary flow, left ventricular developed pressure, and its first derivative also was observed. In the initial phase of reperfusion, NO production measured by 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, respectively. 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↗
PubMed2006

Dietary supplements and related products: a brief summary.

We were gratified by the interest expressed in publishing a large number of presentations from the NIDA organized Workshop on "Natureceuticals (Natural Products), Nutraceuticals, Herbal Botanicals, Psychoactives: Drug Discovery and Drug-Drug Interactions". The number of manuscripts received necessitated two volumes of proceedings. In this brief summary of the second volume, we present an introduction to the roles of organizations such as National Center for Complementary and Alternate Medicine and Office of Dietary Supplements, both at the National Institutes of Health, and the Food and Drug Administration. These agencies are involved in research and regulation of dietary supplements and related products. Next, a brief summary of each of the fifteen articles is provided. The first four articles are related to regulatory and standardization aspects: issues related to botanicals (Khan); USP and dietary supplements (Srinivasan); dietary supplement reference materials (Sander et al.); and proposed cGMPs and the scientific basis behind the proposed regulations by FDA (Melethil). The next three articles relate to the methodologies employed in research: LC/MS for the pharmacokinetic analysis polyphenols from dietary supplements (Barnes et al.); proteomic analysis of grape seed extract (Kim et al.); and a nematode model, C. elegans, in Alzheimer's and ginkgo biloba extract for mechanistic studies; another model, a hepatocyte tissue culture model for drug herbal interaction, is reviewed later and presented by Venkataramanan. The next four chapters are on specific dietary supplements: green tea and the polyphenolic catechins (Zaveri); curcumin (Maheswari et al.); tocotrienols (alpha-tocotrienol, Sen and Roy), gamma-tocotrienol (Sree Kumar et al.). This topic is followed by drug interaction studies: in vitro and in vivo assessment methodologies (Venkataramanan); flavonoid-drug interactions (Morris); MDR and CYP3A4-mediated drug-herb interaction (Pal and Mitra); and evidence-based examination of drug-herb interaction (Chavez and Chavez).

Complementary Therapies↗
PubMed2006

Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study.

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50-80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.

Aged↗
PubMed2004

Ginkgo biloba promotes short-term retention of spatial memory in rats.

This study examines possible interactions between exposure to Ginkgo biloba extract and enriched environments on the acquisition and retention of spatial learning following massed and spaced trials. After 4 weeks of exposure to either ginkgo or vehicle, 8-week-old rats were tested using a Morris Water Maze in either massed or spaced trials. While ginkgo did not have an effect on maze acquisition or long-term retention, it did promote short-term retention of spatial memory. Following reversal training, ginkgo promoted short-term retention for two groups but impaired retention for a third. These results suggest that ginkgo has powerful effects on short-term retention that vary with training conditions.

Animals↗
PubMed1991

Seasonal Variations of the Flavonoid Content from Ginkgo biloba Leaves.

An HPLC method for the separation and the quantitative determination of flavonol glycosides, acylflavonol glycosides, and biflavones in crude leaf extracts from GINKGO BILOBA is described. The results, expressed in percentage of rutine, kaempferol P-coumaroyl glucorhamnoside, and bilobetin showed a higher amount of acylflavonol glycosides in buds, of flavonol glycosides in spring leaves, and of biflavones in autumn leaves.

Journal Article↗
PubMed2026

Ginkgo biloba versus desmopressin in treatment of children with monosymptomatic nocturnal enuresis: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) compared with Desmopressin and their combination in children with monosymptomatic nocturnal enuresis (MNE). METHODS: In this double-blind, randomized, placebo-controlled trial, 398 children aged 5-14 years with MNE were assigned to four groups: placebo, GBE (60 mg daily), Desmopressin (0.2 mg daily), or GBE plus Desmopressin for 3 months. Primary outcomes included the number of wet nights per week. Secondary outcomes assessed sleep quality using the Sleep Disturbance Scale for Children (SDSC), arousal by the Disorders of Arousal (DA) score, and quality-of-life using the Pediatric Incontinence Questionnaire (PinQ). RESULTS: After 3 months, the combination group demonstrated the greatest improvement in wet nights (median 0 [IQR 0-2]) compared to GBE (6 [0.5-6.5]) and Desmopressin (2 [0-6]) (p < 0.001). Full response rates (&#x2265;90% reduction in wet nights) were highest with combination therapy (88.3%), followed by Desmopressin (46.5%), GBE (24.8%), and placebo (9.5%) (p < 0.001). GBE-containing groups showed significantly increased DA and SDSC scores, indicating enhanced arousal and lighter sleep. Quality-of-life (PinQ) score decreased in all treatment groups denoting improvement, with the best outcomes observed in the combination arm. Adverse effects were mild and comparable across groups, and serum sodium levels remained stable. CONCLUSION: GBE is a safe and effective novel therapy for MNE, improving sleep arousal and symptom control. Its combination with Desmopressin offers superior efficacy, better quality of life, and lower relapse rates than either agent alone.

Humans↗
PubMed1988

Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia.

The purpose of the present study was to approach the compound(s) responsible for the beneficial effects of an extract of Ginkgo biloba leaves (EGB) on animals subjected to hypoxia. In this first approach we compared the effects of the flavone and the non-flavone fraction of EGB with those of the whole extract on mice in lethal hypoxia (3.5% O2), on brain energy metabolism of artificially ventilated rats inspiring 7% O2, and on local cerebral blood flow (LCBF) of normoxic rats. The latter two experimental settings should also extend the knowledge about the underlying mechanisms of the antihypoxidotic actions. EGB as well as its non-flavone fraction considerably prolonged the survival time of mice under lethal hypoxia. EGB retarded the breakdown of brain energy metabolism in the hypoxic artificially ventilated rat. A corresponding effect was exerted by the non-flavone fraction while the flavone fraction even worsened the metabolic state. The non-flavone fraction increased LCBF in the majority of 35 examined brain regions; a similar effect could be seen after EGB-treatment, while the flavone fraction caused only minor alterations of LCBF. We conclude that the non-flavone fraction of EGB carries the antihypoxidotic activity. Metabolic effects are suggested to cause this activity. Further studies are necessary to elucidate the effective compound within this fraction.

Animals↗
PubMed2001

[Separation and quantitative analysis of ginkgolic acids from Ginkgo biloba leaves by reverse phase argentation high performance liquid chromatography].

AIM: To develop a reverse phase argentation high performance liquid chromatographic (RP-AHPLC) method for the separation and determination of ginkgolic acids. METHODS: Liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS) was applied to identify ginkgolic acids from Ginkgo biloba leaves and four ginkgolic acids of the samples were separated and quantified by RP-AHPLC. Leaves were extracted with ethanol and analytes were extracted with hexane after addition of acid/salt solution and adsorbent to matrix solution. Ginkgolic acids were separated and determined within 30 minutes by RP-AHPLC under optimum chromatographic conditions. Methanol and 5% aqueous acetic acid (90:10) containing 0.03 mol.L-1 silver ion was used as mobile phase, column temperature was selected at 30 degrees C, flow rate was 1.0 mL.min-1, UV detection wavelength was at 310 nm. The spectra analysis and purity identification of chromatographic peaks of ginkgolic acids were further confirmed by means of diode array detection. RESULTS: Four ginkgolic acids were baseline separated from each other and from other interfering components. The average recovery and relative standard deviation of the method were 97.3% and 1.6%, respectively. CONCLUSION: RP-AHPLC was an excellent method for separation of homologous with different carbon atom numbers and double bond. The method is useful for the quality control of extract of Ginkgo biloba leaves.

Chromatography, High Pressure Liquid↗
PubMed2003

[Studies on supercritical CO2 fluid extraction for ginkgolic acids in the epicarp of Ginkgo biloba].

The technology of supercritical CO2 fluid extraction for ginkgolic acids in the epicarp of Ginkgo biloba L. was studied. The effect of pressure, temperature and extraction time on the yield of the ginkgolic acids was explored. The optimum conditions for supercritical CO2 fluid extraction was 30 MPa, 45 degrees C, extraction time 6 h and the flow rate of CO2 2L/min. The ginkgolic acids were determined by HPLC. Supercritical CO2 fluid extraction exceled the traditional solvent extraction in high yield, high purification and easy operation.

Carbon Dioxide↗
PubMed2004

Determination of ginkgolide A, B, and bilobalide in biloba L. extracts by microdialysis-HPLC.

A method has been developed for measuring ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts by using a self-assembled microdialysis device coupled on-line to high-performance liquid chromatography. The optimal conditions for dialysis efficiency and chromatographic analysis were investigated. The results show that the dialysis efficiencies for ginkgolide A, B, and bilobalide are 97.8-100.4%. For the spike concentration of 45 mg L(-1), the recoveries of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts were at 97-100.7% with 3.1-4.7% RSD. The proposed method has therefore been shown to be applicable to the analysis of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts.

Calibration↗
PubMed1998

The sensitizing capacity of ginkgolic acids in guinea pigs.

BACKGROUND: Ginkgo biloba possesses fruits that have caused numerous cases of allergic contact dermatitis. Low amounts of the ginkgolic acids occur in the leaves as well. OBJECTIVE: Leaf extracts are used to treat cerebrovascular and peripheral vascular disorders. The question arises whether skin hypersensitivity reactions may be adverse effects because the pharmaceutical preparations contain low amounts of ginkgolic acids. METHODS: Guinea pigs were sensitized experimentally with pure ginkgolic acids as well as with leaf extracts containing approximately 1,000 ppm of ginkgolic acids. RESULTS: The guinea pigs could be sensitized successfully with the pure ginkgolic acids. The animals could not be sensitized with the leaf extract. CONCLUSION: Leaf extracts of Ginkgo biloba taken orally or given by infusion to treat diffuse cerebral disturbances can be considered safe, even when they might contain up to 1,000 ppm of the sensitizing ginkgolic acids.

Administration, Oral↗
PubMed2005

Development of a ginkgo biloba fingerprint chromatogram with UV and evaporative light scattering detection and optimization of the evaporative light scattering detector operating conditions.

A fingerprint chromatogram of a standardized Ginkgo biloba extract is developed on a monolithic silica column using a ternary gradient containing water, iso-propanol and tetrahydrofuran. For the detection, UV and evaporative light scattering (ELS) detectors are used, the latter allowing detection of the poor UV absorbing compounds as ginkgolides (A-C and J) and bilobalide in the extract. The complementary information between the UV and ELS fingerprint is evaluated. The ELS detector used in this study can operate in an impactor 'on' or 'off' mode. For each mode, the operating conditions such as the nebulizing gas flow rate, the drift tube temperature and the gain are optimized by use of three-level screening designs to obtain the best signal-to-noise (S/N) ratio in the final ELS fingerprint chromatogram. In both impactor modes, very similar S/N ratios are obtained for the nominal levels of the design. However, optimization of the operating conditions resulted, for both impactor modes, in a significant increase in S/N ratios compared to the initial evaluated conditions, obtained from the detector software.

Chromatography, High Pressure Liquid↗
PubMed2002

Inhibition of intracellular calcium elevation and blunting of vasopressor response due to serotonin by ginkgolide B.

The vascular effects of each individual composition in the extract of Ginkgo biloba have not been clarified. In this work, we have investigated whether ginkgolide B (GKB), a terpene lactone component from Ginkgo biloba, modulates intracellular calcium ([Ca (2+)] i) of vascular smooth muscle cells (smc) and how it influences the vasopressor response in vitro caused by serotonin (5-HT). GKB (3.2 - 9.6 microM) selectively decreased serotonin-induced [Ca (2+)] i elevations in cultured smc from bovine aorta in dose-dependent manner, while it had no effects on both resting [Ca (2+)] i and potassium-elicited [Ca (2+)] i elevations. On the other hand, GKB in a concentration of 3.2 - 9.6 microM moderately decreased the maximal pressor efficacy of serotonin by 14 - 45 % in rat mesenteric vascular beds, and the EC50 remained unchanged. The comparison study also showed GKB had no effects on noradrenaline-elicited pressor reactions. These results implicate that GKB may selectively inhibit serotonin-mediated [Ca (2+)] i mobilization in vascular smc and non-competitively alleviate the vasopressor effect of serotonin in vitro.

Animals↗
PubMedDate not supplied

Ginkgo biloba (EGb 761) in the treatment of equilibrium disorders.

In an open, controlled study, 44 patients complaining of vertigo, dizziness, or both, caused by vascular vestibular disorders were randomly treated with extract of Ginkgo biloba (EGb 761) 80 mg twice daily or with betahistine dihydrochloride (BI) 16 mg twice daily for 3 months. A complete neuro-otologic and equilibrimetric examination was performed at baseline and after 3 months of treatment, with evaluation of clinical findings. In the first month of therapy, vertigo and dizziness improved in 64.7% of patients treated with BI and in 65% of those who received EGb 761. Compared to baseline, no statistically significant changes were observed in cranial scans for patients with a "central" cranial pattern. Likewise, no changes versus baseline were observed in both groups for the equilibrium score. The comprehensive test battery showed the following findings: EGb 761 induced a slight decrease of saccadic delay and considerably increased saccadic velocities; BI improved saccadic accuracy but did not modify delay; EGb 761 improved smooth pursuit gain at 0.4 Hz 40 degrees/s three times more than BI; both drugs asymmetrically reduced nystagmus maximum velocity at 40 degrees/s; both drugs asymmetrically improved the sinusoidal vestibulo-ocular reflex; BI considerably reduced--whereas EGb 761 considerably improved--visuovestibular ocular reflex. No side effects were recorded during the trial except for transient mild headache and gastric upset in 2 patients receiving EGb 761 and transient cyanosis of nails and lips in 1 patient given BI. These results suggest that EGb 761 and BI operate at different equilibrium receptor sites and show that EGb 761 can considerably improve oculomotor and visuovestibular function.

Aged↗
PubMed1987

Involvement of platelet-activating factor (PAF) in cerebral post-ischemic phase in Mongolian gerbils.

Platelet-activating factor (PAF) is a potent mediator of anaphylaxis and shock. In addition, evidence for PAF participation in gastric, intestinal and heart post-ischemic phase has been recently demonstrated. Ginkgo biloba extracts improve cerebral metabolism and protect brain against hypoxic damage in various models of cerebral ischemia. Potent and specific antagonists of PAF have been found in Ginkgo biloba and termed Ginkgolides: BN 52020, BN 52021, BN 52022, BN 52024. We therefore undertook the investigation of the role of Ginkgolides in cerebral ischemia obtained by bilateral ligature of the common carotid for 10 min and 6 h of recirculation in male Mongolian adult gerbils. Given preventively (one week treatment 10 mg/kg/day orally) or at the time of clamping, BN 52021 and related Ginkgolides dose-dependently antagonize morbidity assessed by the stroke-index. Similarly the mitochondrial respiration evaluated by the respiratory control ratio is significantly improved. In both determinations, the range of activity: BN 52021 greater than, BN 52020 greater than BN 52022 greater than BN 52024 shows that the effect of Ginkgolides in cerebral ischemia are correlated with their PAF antagonistic properties. Given curatively, 1 h after declamping, BN 52021 is able to reverse the cerebral impairment trend. Kadsurenone and brotizolam, two other chemically unrelated PAF antagonists led to similar recovery. Therefore PAF appears to play an important role in the post-ischemic phase after bilateral carotid ligation in Mongolian gerbils.

Animals↗