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PubMed2005

In vivo biodistribution of ginkgolide B, a constituent of Ginkgo biloba, visualized by MicroPET.

The in vivo dynamic behavior of ginkgolide B (GB), a terpene lactone constituent of the Ginkgo biloba extracts, in the living animal was visualized by positron emission tomographic (PET) imaging using a GB analogue labeled with the positron emitter (18)F. The in vivo imaging studies, combined with ex vivo dissection experiments, reveal that GB exists in 2 forms in the body: the original GB with its lactone rings closed and a second form with one of the rings open. The original GB in plasma is taken up rapidly by various organs including the liver, the intestine and possibly the stomach. Consequently, in plasma, the proportion of the ionized form of GB increases dramatically with time. Thereafter the ratio between the 2 forms appears to shift slowly towards equilibrium. The results suggest that more attention needs to be focused on in vivo dynamics between the 2 forms of GB.

Animals↗
PubMed2004

Recent pharmacological studies on natural products in China.

Natural products have been used as medicinal agents for many years. In addition, these compounds have also served as the starting points for semisynthetic analogs with improved properties. This review focuses on recent advances in the pharmacological studies on natural products mainly performed and published in China. Emphasis will be placed on those compounds that show the greatest promise clinically such as huperzine A (9-amino-13-ethylidene-11-methyl-4-azatricyclo[7.3.1.0(3.8)]trideca-3(8),6,11-trien-5-one), s-(-)-3-n-butylphthalide (s-(-)-3-butyl-1(3H)-isobenzofuranone), (-)-clausenamide (3-hydroxy-4-phenyl-5a-hydroxybenzyl-N-methyl-gamma-lactam) and Ginkgo biloba extract and its active components.

Alkaloids↗
PubMed1999

Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.

Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates O(-)(2). formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 microM 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-L-cysteine (NAC), and Ginkgo biloba extract. Inhibition of MAP kinase with PD-98059 failed to block enhanced O(-)(2). formation by 5-HT. Chinese hamster lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter and receptor activity, showed a similar response to 5-HT (i.e., enhanced mitogenesis, O(-)(2). formation, and ERK1 and ERK2 phosphorylation and activation). Unlike SMCs, they also responded to 5-HT receptor agonists. We conclude that downstream signaling of MAP kinase is a generalized cellular response to 5-HT that occurs secondary to O(-)(2). formation and may be initiated by either the 5-HT transporter or receptor depending on the cell type.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1987

Effect of ginkgolide PAF-acether antagonists on arterial thrombosis.

Topical superfusion by PAF-acether over a branch of the mesenteric artery of the guinea pig invariably results in the formation of a platelet thrombus, adhering onto a denuded area of the vessel wall, or at sites where local retraction of the endothelial cells has occurred. It is demonstrated that the application of exogenous PAF-acether triggers a process of local autogeneration and release of endogenous PAF-acether (or PAF-like substances), maintaining a long phase of sequential regrowth and embolization of thrombi, eventually leading to a complete occlusion of the arterial lumen. Extracts of Ginkgo biloba, administered intravenously or in topical superfusion, inhibit both exogenous- and endogenous-induced thromboformation.

Animals↗
PubMed1999

A review of nutrients and botanicals in the integrative management of cognitive dysfunction.

Dementias and other severe cognitive dysfunction states pose a daunting challenge to existing medical management strategies. An integrative, early intervention approach seems warranted. Whereas, allopathic treatment options are highly limited, nutritional and botanical therapies are available which have proven degrees of efficacy and generally favorable benefit-to-risk profiles. This review covers five such therapies: phosphatidylserine (PS), acetyl-l-carnitine (ALC), vinpocetine, Ginkgo biloba extract (GbE), and Bacopa monniera (Bacopa). PS is a phospholipid enriched in the brain, validated through double-blind trials for improving memory, learning, concentration, word recall, and mood in middle-aged and elderly subjects with dementia or age-related cognitive decline. PS has an excellent benefit-to-risk profile. ALC is an energizer and metabolic cofactor which also benefits various cognitive functions in the middle-aged and elderly, but with a slightly less favorable benefit-to-risk profile. Vinpocetine, found in the lesser periwinkle Vinca minor, is an excellent vasodilator and cerebral metabolic enhancer with proven benefits for vascular-based cognitive dysfunction. Two meta-analyses of GbE demonstrate the best preparations offer limited benefits for vascular insufficiencies and even more limited benefits for Alzheimer's, while "commodity" GbE products offer little benefit, if any at all. GbE (and probably also vinpocetine) is incompatible with blood-thinning drugs. Bacopa is an Ayurvedic botanical with apparent anti-anxiety, anti-fatigue, and memory-strengthening effects. These five substances offer interesting contributions to a personalized approach for restoring cognitive function, perhaps eventually in conjunction with the judicious application of growth factors.

Acetylcarnitine↗
PubMed2005

[The situation of patients with dementia may be rectified by Ginkgo biloba. Results of a health services research study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs].

UNLABELLED: BACKGROUND AND ISSSUES: Ginkgo biloba-extracts are often used in therapy of patients with dementia. In this study, benefit and structure of Ginkgo biloba-extract EGb 761 in treatment of patients with dementia was examined. PATIENTS AND METHODS: For the assessment of quality of life of care-taking relatives and patients as well as treatment costs were documented. The study was conducted as a non-randomised, two-armed cohort study with an open design for 683 slightly or moderately demented patients, aged between 65 and 80 years. Society's perspective was taken. Barthel-Index and MMST were also documented. Because of significant differences at inclusion of both cohorts, a matched-pairs-analysis and multiple regression analysis conducted. RESULTS: According to PLC a significant improvement in quality-of-life of care-taking relatives (p < 0.001) and patients (positive mood p = 0.018, negative mood p < 0.001) was only observed in the Ginkgo-cohort. Also Barthel-Index indicated an improvement in the Ginkgo-cohort (p < or = 0,001). MMST-scores increased significantly only in the Ginkgo-cohort (p < 0.001). Average total cost per patient amounted to 3.614,75 euro in the standard-cohort, whereas these costs per patient in the Ginkgo-cohort amounted to 3.031,78 euro (p = 0.067). Results were confirmed by matched-pairs-analysis. RESULTS: Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attributes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.

Activities of Daily Living↗
PubMed1999

Ginkgo biloba inhibits hydrogen peroxide-induced activation of nuclear factor kappa B in vascular endothelial cells.

The present study determined the effects of Ginkgo biloba extract (GBE) on the activation of nuclear factor kappa B (NF-kappaB) and the level of hydrogen peroxide (H2O2) in bovine pulmonary artery endothelial cells (PAEC). H2O2 showed a concentration-dependent activation of NF-kappaB. GBE demonstrated a concentration-dependent suppression of NF-kappaB activated by H2O2. GBE directly scavenged H2O2 in a cell-free system; it also decreased H2O2 levels in PAEC. These results suggest that the inhibitory effect of GBE on H2O2-induced NF-kappaB activation may be caused by its scavenging and suppression of H2O2. Our experiments demonstrate that GBE can inhibit NF-kappaB activation induced by H2O2 and may thus be effective for the prevention or treatment of atherosclerosis and other disorders related to NF-kappaB activation.

Animals↗
PubMed2004

Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat.

Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain, such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and capsaicin-induced paw licking and in the model of acute gastric damage induced by indomethacin. The agent showed marked anti-inflammatory activity in the carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after carrageenan challenge. The agent was also active p.o. in acute inflammation caused by carrageenan. The administration of GbE with indomethacin, rofecoxib, celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin-induced hind paw licking time and was similarly effective in the hot-plate assay of nociception. In contrast, when assessed in the tail-electric stimulation test, GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical value as an anti-inflammatory and analgesic drug alone or in conjunction with NSAIDs.

Analgesics↗
PubMed2001

Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory.

A computerized test battery was used in a double-blind design to assess the cognitive effects of a nutrient compound containing Ginkgo biloba in 24 normal adults. Ten tasks (perceptual, attention and short-term memory) were presented in a standardized manner designed to maximize performance, with substantial pre-test practice employed to minimize response variability. Subjects were given either placebo or Ginkgo biloba extract capsules to consume for 14 days, after which they performed all tasks twice. They then received the other condition, and after 14 days completed the final test session. Response time and error rate stabilized after pre-test practice. A 'working memory capacity' paradigm demonstrated a reliable 50 ms response time decrease between the placebo and Ginkgo biloba testing, suggesting that Ginkgo biloba speeds short-term working memory processing in normal adults. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2006

Experimental model to assess possible medicinal herb interaction with a radiobiocomplex: qualitative and quantitative analysis of kidney, liver and duodenum isolated from treated rats.

Ginkgo biloba extract (EGb) has been used as a medicinal herb. Several biological properties have been associated with this extract, especially, in the increase of the blood flow, in the action as platelet activating factor antagonism and in the prevention of the membrane against the damage caused by free radicals. Radiobiocomplexes have been utilized in various nuclear medicine procedures helping in the diagnosis and/or treatment of human diseases. Many substances have been reported to affect the bioavailability of different radiobiocomplexes. The aim of this work was to evaluate the possible influence of an EGb on the bioavailability of the sodium pertechnetate (99mTcO4Na) and on the morphometry of some organs isolated from rats. These animals were treated with EGb and 99mTcO4Na was injected. The animals were sacrificed, the organs isolated, counted in a well counter and the percentage of radioactivity per gram of each organ was calculated. The results showed that EGb decreased the uptake of the 99mTcO4Na in the duodenum (P<0.05). Moreover, morphometric analysis has revealed significant modifications (P<0.05) on kidney, liver and duodenum due to the cited treatment. It is speculated that the substances present in the EGb could act directly or generate metabolites capable to promote changes in organs (kidney, liver and duodenum), however, only significant alteration in the uptake of the 99mTcO4Na in the duodenum.

Animals↗
PubMed1985

[Double blind study of the hypoxia protective effect of a standardized Ginkgo biloba preparation after repeated administration in healthy subjects].

A randomised, placebo-controlled, double-blind, crossover study was run in 8 healthy, male subjects (mean age 27.3 +/- 2.6 years, mean BW 75.3 +/- 9.7 kg) to demonstrate a possible hypoxia-protective effect of standardised Ginkgo flavone glycosides after subchronical administration. After a 14-days' treatment with Ginkgo bilobae extract (Tebonin) performance of subjects was studied--concerning assessments of oculomotor and complex choice reaction system as well as simple cardiorespiratory parameters under multiple exposure to hypoxic hypoxia (10.5% oxygen, 89.5% nitrogen)--using oculodynamic methodology (ODT). Hypoxia increased the corneoretinal resting-potential of the eye and stimulated respiration. Both parameters were significantly reduced by verum administration. Under cumulative exposure to hypoxic hypoxia fixation time of saccadic eye movements and complex choice reaction time were significantly improved by Ginkgo flavone glycosides vs placebo. These results could be explained as a hypoxia-protective phenomenon--supporting the therapy of cerebral insufficiency.

Adult↗
PubMed2002

The use of Ginkgo biloba in Raynaud's disease: a double-blind placebo-controlled trial.

Raynaud's phenomenon (RP) is a common and painful condition characterized by episodic digital ischaemia produced by emotion and cold. Treatment of RP is notoriously difficult because of the high incidence of side effects. The aim of our study was to investigate the clinical efficacy of a standardized Ginkgo biloba extract (Seredrin) in the treatment of RP in patients with no apparent, associated condition such as systemic sclerosis. A two-week assessment period was done during which patients were asked to record frequency, severity and duration of attacks in diaries. Subjects were then randomized independently of the study centre to receive either active or placebo treatment for 10 weeks, during which time the same data were recorded in their diaries. Patients were seen after two and four weeks of treatment and at the end of the 10-week treatment phase. Blood samples pre- and post-treatment were taken for haemorrheology. Only in the number of attacks per day was there a significant effect of treatment over placebo. The number of attacks per week prior to treatment with Seredrin was 13.2 +/- 16.5 reducing to 5.8 +/- 8.3, a reduction of 56%, whereas placebo reduced the number by only 27% (p < or = 0.00001). There were no significant differences in haamorrheology between the two groups. Ginkgo biloba phytosome may be effective in reducing the number of Raynaud's attacks per week in patients suffering from Raynaud's disease.

Adolescent↗
PubMed2002

Influence of pharmaceutical quality on the bioavailability of active components from Ginkgo biloba preparations.

To be effective, herbal medicinal products are expected to meet comparable standards concerning the assessment of efficacy, safety and biopharmaceutical quality as chemically defined synthetic drugs as food supplements. However, these requirements are often not fulfilled, particularly regarding the characterization of biopharmaceutical properties such as in-vitro dissolution and in-vivo bioavailability. With respect to the relevance of biopharmaceutical quality of herbal medicinal products, two different Ginkgo biloba brands (test product: Ginkgo biloba capsules; reference product: Ginkgold) were analysed for dissolution rates and bioavailability of the most relevant active ingredients. Dissolution rates at pH 1 and 4.5 were determined according to the USP 23. The relative bioavailability of ginkgolide A, ginkgolide B and bilobalide was investigated after single oral administration of 120 mg Ginkgo biloba extract as tablets or capsules. Bioavailability data (area under the curve and peak concentration in plasma) were clearly different and did not show bioequivalence of test and reference products. The slow in-vitro dissolution of the test product resulted in a large decrease in bioavailability. These results indicate for the first time that the pharmaceutical properties of a herbal medicinal product have a significant impact on the rate and extent of drug absorption, and very likely on efficacy in humans.

Administration, Oral↗
PubMed2006

Plaque-derived oxidative stress mediates distorted neurite trajectories in the Alzheimer mouse model.

Alzheimer disease (AD) is characterized both by senile plaques and neurodegeneration, although the details of the relationship between the 2 are not well understood. We postulated that oxidative stress resulting from senile plaques may mediate plaques' effects on local neuronal processes. Using multiphoton microscopy, we directly demonstrate the generation of reactive oxygen species by senile plaques. After screening of several natural antioxidants ex vivo, we assessed in vivo the effect of 2 orally administered antioxidants in APPswe/PS1d9 transgenic mice. Both Ginkgo biloba extract and vitamin E reduced the oxidative stress resulting from senile plaques in vivo as monitored with intracranial imaging. Both treatments also lead to a progressive reversal of the structural changes in dystrophic neurites associated with senile plaques. These results suggest a causal relationship between plaque-associated oxidative stress and neuritic alterations and demonstrate for the first time that the focal neurotoxicity associated with the senile plaques of AD is partially reversible with antioxidant therapies. The quantitative ex vivo screen combined with in vivo monitoring of efficacy should lead to more effective clinical therapies for the prevention of oxidative stress and neurotoxicity in AD.

Alzheimer Disease↗
PubMed1980

Effects of Ginkgo Biloba on changes induced by quantitative cerebral microembolization in rats.

Unilateral embolization of the brain was performed in rats by the intracarotid injection of 4000 radioactive microspheres (50 micron). The local blood flow was determined using the iodoantipyrine technique in the hippocampus, hypothalamus, striatum and remainder of the brain. Embolization resulted in a decrease in the blood flow and a modification of the distribution of microflow. Besides, the embolization produced changes in energy metabolism, specially a fall in ATP and glucose levels and an increase in lactate level. Subsequently severe vasogenic cerebral edema developed. There was a correlation between the number of microspheres injected and the extent of edema. Pretreatment with an extract of Ginkgo Biloba leaves partially suppressed the effects of the embolization. An increase in the blood flow associated with normalization of cellular energy metabolism explained the decrease in brain edema.

Adenosine Triphosphate↗
PubMed2006

The psychopharmacology of European herbs with cognition-enhancing properties.

Extensive research suggests that a number of plant-derived chemicals and traditional Oriental herbal remedies possess cognition-enhancing properties. Widely used current treatments for dementia include extracts of Ginkgo biloba and several alkaloidal, and therefore toxic, plant-derived cholinergic agents. Several non-toxic, European herbal species have pan-cultural traditions as treatments for cognitive deficits, including those associated with ageing. To date they have not received research interest commensurate with their potential utility. Particularly promising candidate species include sage (Salvia lavandulaefolia/officinalis), Lemon balm (Melissa officinalis) and rosemary (Rosmarinus officinalis). In the case of sage, extracts possess anti-oxidant, estrogenic, and anti-inflammatory properties, and specifically inhibit butyryl- and acetyl-cholinesterase. Acute administration has also been found to reliably improve mnemonic performance in healthy young and elderly cohorts, whilst a chronic regime has been shown to attenuate cognitive declines in sufferers from Alzheimer's disease. In the case of Melissa officinalis, extracts have, most notably, been shown to bind directly to both nicotinic and muscarinic receptors in human brain tissue. This property has been shown to vary with extraction method and strain. Robust anxiolytic effects have also been demonstrated following acute administration to healthy humans, with mnemonic enhancement restricted to an extract with high cholinergic binding properties. Chronic regimes of aromatherapy and essential oil respectively have also been shown to reduce agitation and attenuate cognitive declines in sufferers from dementia. Given the side effect profile of prescribed cholinesterase inhibitors, and a current lack of a well tolerated nicotinic receptor agonist, these herbal treatments may well provide effective and well-tolerated treatments for dementia, either alone, in combination, or as an adjunct to conventional treatments.

Alzheimer Disease↗
PubMed2002

[Hepatic injury induced by acute lung injury in aging rats].

OBJECTIVE: To investigate the induction of hepatic function damage by acute lung injury (ALI) in aging rats and the effect of Ginkgo Biloba extract (GBE) on this process. METHODS: Thirty male Wistar rats were used to produce the aging animal model. Aging rats were randomly divided into three groups: the control group, the lipopolysaccharide (LPS, intravenous injection) group, and the GBE + LPS group (GBE given 7 days before experiment, once a day, via the esophagus). Samples from the blood, the lung and the liver were collected 2 and 6 h after LPS or saline administration. RESULTS: ALI was induced by intravenous injection of LPS in aging rats. Compared with the aging control, the total bilirubin content and the glutamic pyruvic transaminase (GPT) activity in serum did not change at 2 h after LPS administration. But at 6 h, they were increased, respectively from (10.9 +/- 0.6) mg/L and (26 +/- 3) U in the control group to (30.1 +/- 2.1) mg/L and (88 +/- 12) U in the LPS group (P < 0.001). MDA content increased in the blood and the lung tissue at 2 has compared to the control group, from (15.9 +/- 1.8) micro mol/L and (18.8 +/- 2.1) nmol/mg protein to (22.1 +/- 1.9) micro mol/L and (28.8 +/- 3.1) nmol/mg protein (all P < 0.001), respectively. SOD activity in the lung tissue was decreased significantly, from (25.5 +/- 2.6) mU/L and (36.1 +/- 2.4) U/mg protein to (20.6 +/- 1.9) mU/L and (32.0 +/- 2.7) U/mg protein, respectively (P < 0.05, P < 0.001). The GSH-P(X) activity and the Na(+)-K(+)-ATPase activity in the lung tissue at 2 hours after LPS administration were decreased markedly, from (28.2 +/- 2.8) U/mg protein and (4.9 +/- 0.5) micromol Pi x mg(-1) protein x h(-1). to (21.1 +/- 2.7) U/mg protein and (3.1 +/- 0.3) micromol Pi x mg(-1) protein x h(-1). These changes lasted 6 h after LPS administration. These parameters did not change significantly in the hepatic tissue at 2 h after LPS administration. But after 6 h, MDA content was increased from (7.9 +/- 0.9) nmol/mg protein to (10.9 +/- 0.7) nmol/mg protein; while the GSH-P(X) and the Na(+)-K(+)-ATPase activities were decreased markedly, from (59.0 +/- 3.9) U/mg protein and (0.87 +/- 0.04) micromol Pi x mg(-1) protein x h(-1) to (49.2 +/- 3.0) U/mg protein and (0.77 +/- 0.04) micromol Pi x mg(-1) protein x h(-1) (P < 0.001, P < 0.01). There was no obvious change in the SOD activity. All the changes were significantly attenuated in the GBE + LPS group (P < 0.05, P < 0.01). CONCLUSION: Hepatic function damage could be induced by ALI in aging rats. GBE showed a protective effect on ALI and hepatic function damage in this animal model.

Aging↗
PubMed2000

In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides.

Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes. Various flavonoids including anthocyanosides and ginkgo biloba extracts have been shown to be effective against experimentally induced capillary hyperfiltration. The aim of the present study was to test the effects of anthocyanosides on capillary filtration in diabetic rats. For this purpose, we have validated the use of our previously described in vivo method for measurement of the capillary filtration of albumin (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium myrtillus (group B), or no treatment (group C). The isotopic test of CFA consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing venous compression on a hindquarter, and measuring radioactivity externally on the limb before, during, and after removal of venous compression. After removal of the tourniquet, the radioactivity curve decreased. Interstitial albumin retention (AR) and the ratio of the amplitudes of the low- and high-frequency peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier transform of the last part of the radioactivity curve, were calculated. In STZ-treated animals, the isotopic test was performed at a mean age of 97 days (time 1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12 weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic groups than in the control rats, without a significant difference between these groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In group C, AR increased significantly (P < .0005) from time 1 to time 3. In group A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the LF/HF ratio significantly increased with time (P < .0005) and the levels at time 3 were significantly higher versus control rats (P < .0001). In group B, the LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values found in the control rats. In conclusion, these data show that (1) this new in vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic rats, (2) it is reproducible and may be repeated over several months to evaluate spontaneous microcirculatory changes, and (3) anthocyanosides appear to be effective in preventing the increase in CFA and the failure of lymphatic uptake of interstitial albumin in diabetic animals.

Animals↗