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PubMed1991

The inhibitory effect of plant extracts on the collagenolytic activity and cytotoxicity of human gingival fibroblasts by Porphyromonas gingivalis crude enzyme.

It is well known that plant extracts inhibit some enzymatic activities. The present study examined the inhibitory effects of natural plant extracts against the collagenolytic activity of Porphyromonas gingivalis. The enzyme was isolated from a culture supernatant of P. gingivalis 381. The aqueous and 50% ethanolic extracts of Ginkgo biloba, Mosla chinensis, Salvia officinalis, Cinnamomum cassia, and a catechin extract of Camellia sinensis exhibited strong inhibitory effects on collagenolytic activity. The activities of these plant extracts were higher than that of tetracycline-HCl. They also inhibited the cytotoxicity of P. gingivalis crude enzyme against human gingival fibroblasts. C. sinensis catechin was the most effective agent in neutralizing the cytotoxicity of P. gingivalis. The aqueous and 50% ethanolic extracts of C. cassia had relatively strong anti-cytotoxic activity. Although the other samples strongly inhibited the collagenolytic activity of P. gingivalis, they were not effectively anti-cytotoxic. The present findings suggest that C. sinensis and C. cassia extracts are effective in reducing the pathogenicity of periodontopathic bacteria.

Catechin↗
PubMed1999

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical.

BACKGROUND: A study was carried out to investigate the effect of two antioxidants--Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)--in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. METHODS: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 microliters of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n = 8) did not receive any treatment and served as a positive control. Groups 2 (n = 8) and 3 (n = 8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n = 4) was treated by three intramuscular injections of 15,000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. RESULTS: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. CONCLUSION: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Administration, Oral↗
PubMedDate not supplied

Effects of Ginkgo biloba on mental functioning in healthy volunteers.

BACKGROUND: There has been a lack of investigations examining the effects of Ginkgo biloba extract EGb 761 on mental functions and quality of life in healthy subjects with no cognitive impairment. Thus, the objective of the present study was to evaluate the relatively short-term (i.e., 4 weeks) effects of EGb 761 on mental functioning and quality of life in healthy volunteers. METHODS: The trial was conducted as a 4-week, randomized, double-blind, placebo-controlled, parallel-group, monocentric study. Sixty six healthy volunteers aged between 50 and 65 years without age-associated cognitive impairment were randomized, 32 into the placebo and 34 into the EGb 761-treatment group (240 mg, t.i.d.). Safety and compliance were monitored after 1, 2, 3 and 4 weeks. Primary outcome measures in this study are the subjects' judgment of their own mental health (MH), their general health (GH) and their quality of life (QoL) operationalized on the basis of three different visual analog scales (VAS). Secondary outcome measures are 15 tests and experimental procedures based on a neurobiologically based classification or taxonomy of functions. RESULTS: Intergroup differences in self-estimated mental health as well as self-estimated quality of life were significant in favor of EGb 761. No intergroup differences were found in self-estimated general health. Secondary outcomes supporting the notion of superiority of the active drug were found for both motor performance and emotional evaluation. This study did not reveal evidence of unknown drug-induced side effects or intolerance. No serious adverse events were observed during the study. CONCLUSIONS: Both questions treated in this study, efficacy and safety, are important from a medical perspective because many persons take the agent studied in an effort to enhance their mental functioning and general well-being. The findings of this study support the adequacy of intake of EGb 761 to improve the functions indicated previously.

Aged↗
PubMed2001

[Rational therapy of Alzheimer dementia based on current clinical studies].

Several preparations are currently available for the treatment of Alzheimer's dementia. To date only some of these drugs could show evidence of efficacy that would justify a recommendation for their therapeutic use. In the present survey, the results of five controlled clinical trials with acetylcholinesterase inhibitors versus Ginkgo-biloba extract have been analysed. The trials conducted with the acetylcholinesterase altogether have a larger patient population, an acceptable significance level of therapeutic effect as well as a lower rate of drop outs. Based on the documentation presented here, only the approved acetylcholinesterase inhibitors are currently to be recommended under strict scientific criteria for use in the treatment of Alzheimer's dementia.

Activities of Daily Living↗
PubMed2004

Effect of Tanakan on postischemic activity of protein synthesis machinery in the rat brain.

A growing body of evidence supports the role of free radicals in triggering the functional and metabolic disturbances following transient cerebral ischemia. This study was designed to evaluate whether the extent of reperfusion-induced inhibition of protein synthesis initiation as well as tissue injury can be reduced by Tanakan (Ginkgo biloba extract, EGb 761) (Beaufour-Ipsen Industrie). Rats received Tanakan in the dose of 40 mg/kg/day for 7 days before surgical intervention. Transient forebrain ischemia was induced by 4-vessel occlusion. Rats were subjected to 20 min of ischemia followed by 30 min, 4 h or 7 days of reperfusion. Protein synthesis rate, reinitiation ability and neurodegeneration in the frontal cortex and hippocampus were measured by the incorporation of radioactively labelled leucine into polypeptide chains in postmitochondrial supernatants and by Fluoro-Jade B staining. The protective effect was observed, concerning both the protein synthesis and the number of surviving neurons, in the Tanakan-treated groups. Tanakan significantly reduced the ischemia/reperfusion-induced inhibition of translation in the neocortex as well as in the highly sensitive hippocampus. Our results indicate that free radicals play an important role in the development of reperfusion-induced injury, and the treatment of ischemic and reperfused brain with free radical scavengers may reduce the severity of reperfusion damage.

Animals↗
PubMed2002

The effects of EGb 761 on lipid peroxide levels and superoxide dismutase activity in sunburn.

BACKGROUND/PURPOSE: Free oxygen radicals are involved in inflammatory skin reactions induced by ultraviolet B (UVB). In this study, the effect of a herbal antioxidant Ginkgo biloba extract (EGb 761) was investigated in UVB irradiated mice skin. METHODS: The study was carried out on four groups of mice (n = 6 in each group). The first group was a control group (G1). The second group (G2) was only exposed to acute UVB irradiation. The third group (G3) received 100 mg/kg/day of EGb 761 orally for 5 days before UVB irradiation and the fourth group (G4) was given only a single dose of EGb 761 immediately after UVB irradiation. Eighteen hours after exposing to UVB, lipid peroxide levels, and superoxide dismutase (SOD) activities were studied and UVB damage was evaluated histopathologically according to "sun-burn cell count". RESULTS: The SOD activities and Malondialdehyde (MDA) levels in G2, G3 and G4 were found to be decreased significantly when compared with G1 (P < 0.05). The SOD activities of G3 and G4 were higher when compared with G2 (P < 0.05). The number of sunburn cells (SBCs) was the highest in G2. CONCLUSIONS: Our results suggest that EGb 761 may have an important effect, both as a protective and therapeutic agent, in sunburn after UVB irradiation.

Analysis of Variance↗
PubMed1998

Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil.

Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.

Animals↗
PubMed1999

Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals.

The present study was conducted to evaluate the different effects of the constituents of EGb761 (Ginkgo biloba Extract) on apoptosis in cerebellar granule cells induced by hydroxyl radicals. The total flavonoid component of EGb761, two pure EGb761 components (rutin and quercetin), and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. ESR(electron spin resonance) results showed that the IC50 of the flavonoids for scavenging hydroxyl radicals was almost the same as that of EGb761, even though flavonoids make up only 24% of EGb761, implying that other constituents of EGb761 besides flavonoids can scavenge hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard. Terpenes did not scavenge hydroxyl radicals directly, which might be related to their "cage-like" structures.

Animals↗
PubMed2003

Behavioural and psychological symptoms of dementia (BPSD): effects of EGb 761.

Dementia patients often present with behavioural and psychological symptoms, with prevalence rates reaching 90%. It is therefore important to know whether an antidementia drug that improves cognitive function can also reduce the burden of behavioural and psychological symptoms of dementia, and whether it can improve cognitive function in patients suffering from such non-cognitive symptoms. Therefore, three types of study with Ginkgo special extract EGb 761 (definition see editorial) were reviewed: 1) studies on patients with impairment of cerebral function or dementia associated with behavioural and psychological symptoms (BPSD); 2) studies on patients suffering from impairment of cerebral function and depression; 3) dementia studies on patient samples with a high prevalence of BPSD. Compared to placebo, EGb 761 improved these symptoms significantly in all studies that used a scale to measure the presence and intensity of BPSD. Moreover, EGb 761 was found to be superior to placebo with respect to improvement in cognitive function, daily living activities and global assessment in dementia patients suffering from BPSD. It may be concluded that EGb 761 is of particular interest to patients with dementia and BPSD since it improves both the patient's cognitive ability and behavioural and psychological symptoms.

Activities of Daily Living↗
PubMed2002

A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities.

Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian and Chinese traditional medicine systems. Standardized extracts of B. monniera and G. biloba were used to evaluate the antidementic and anticholinesterase activities in adult male Swiss mice. Antidementic activity was tested against scopolamine (3 mg/kg ip)-induced deficits in passive avoidance test. Three different extracts of B. monniera (30 mg/kg) and extract of G. biloba (15, 30 and 60 mg/kg) were administered postoperatively, daily for 7 days and 60 min after the last dose, i.e., on Day 7, first trial was conducted. In passive avoidance test, increased transfer latency time (TLT) and no transfer response (NTR) were taken as criteria for learning. TLT and NTR were significantly increased and decreased in second trial, 24 h after the first trial in control group and scopolamine-dementia group, respectively. The B. monniera- and G. biloba-treated groups produced significant increase in TLT and NTR on second trial (40-80%) after scopolamine treatment, thus, attenuating its antidementic effect. Both the extracts showed a dose (10-1000 microg)-dependent inhibitory effect on acetylcholinesterase (AChE) activity (in vitro), performed spectrophotometrically. IC(50) of G. biloba was 268.33 microg, whereas none of the extracts of B. monniera showed more than 50% inhibition. At a dose concentration of 30 and 60 mg/kg, extracts of G. biloba showed a cognitive enhancing property and, at the same time, a significant decrease in AChE-specific activity in both per se and scopolamine-dementia groups. These extracts possess a significant anticholinesterase and antidementic properties, which may be useful in the treatment of dementia.

Acetylcholinesterase↗
PubMed2005

Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin.

Quercetin, kaempferol, and isorhamnetin were the most important flavonoid constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo flavonols were performed in Caco-2 cell mono-layers. Their apparent permeability in absorptive and secretion directions was determined, and quercetin, kaempferol and isorhamnetin displayed polarized transport, with the Papp,B-A being higher than the Papp,A-B (P<0.01 for quercetin, P<0.001 for kaempferol and isorhamnetin, Student's t-test). Bcap37/MDR1 cells, which were transfected with a P-glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were lower than those in parent cells (P<0.05 for quercetin, P<0.01 for isorhamnetin, Mann-Whitney U test). The concentrations of the flavonol in transfected cells increased when incubated with the P-gp inhibitor verapamil (P<0.05 for kaempferol, Mann-WhitneyU test). A colorometric assay for ATPase activity was applied to the detection of interaction of flavonol with P-gp. Quercetin and kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase activity (P<0.05 for isorhamnetin, Mann Whitney U test). The results indicated that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P-gp. The P-gp type efflux pump might limit the bioavailability of Ginkgo flavonols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Efficient extraction of ginkgolides and bilobalide from Ginkgo biloba leaves.

An efficient and rapid protocol has been developed for extracting ginkgolides and bilobalide (terpene trilactones) from Ginkgo biloba leaves. The procedure takes advantage of the extraordinary stability of the terpene trilactone structure to a variety of chemical treatments, especially oxidation, despite the presence of multiple oxygen functions. The protocol involves boiling the aqueous extract of leaves with dilute hydrogen peroxide, extraction with ethyl acetate, washing with basic solutions, and charcoal filtration to yield an off-white powder, terpene trilactone content 60-70%. It is likely that the hydrogen peroxide treatment degrades the undesired leaf constituents that lead to intense emulsification during extractions. Further reversed-phase chromatography of the extracts with polymeric resins removes the undesirable ginkgolic acids to amounts less than 10 ppm. The extracts are suited for pure terpene trilactone preparation, enrichment of terpene trilactone content in nutraceuticals, and preparations of low-flavonoid/high-terpene trilactone controls in medicinal studies. The four ginkgolides (ginkgolides A, B, C, J) and bilobalide isolated from the extract were identical in all respects with authentic specimens.

Chromatography, High Pressure Liquid↗
PubMed2004

The effect of Ginkgo biloba in isolated ischemic/reperfused rat heart: a link between vitamin E preservation and prostaglandin biosynthesis.

The effect of Ginkgo biloba extract (EGb 761) was studied in rat hearts submitted to ischemia/reperfusion. Isolated hearts perfused in Langendorff mode were subjected to 60 minutes of global ischemia and 15 minutes of reperfusion. EGb 761 was administered by chronic or acute treatment: intra-peritoneal injections of 5 mg/Kg extract for 5 days, or 100 mg /L extract addition to the perfusion buffer, respectively. In hearts not treated with EGb 761, ischemia induced a 20% decrease in the concentration of membrane alpha-tocopherol. This effect was not worsened by reperfusion. alpha-tocopherol consumption was accompanied by about 650% increase in 6-ketoPGF1alpha release within 3 minutes of reperfusion. Moreover, ischemia induced activation of transcription factor NF-kappaB, as compared with the untreated group. In both chronic and acute treatment with EGb 761, heart concentration of alpha-tocopherol was completely spared during ischemia as much as after reperfusion, and a significant decrease of 6-ketoPGF1alpha release was observed at 3 minutes of reperfusion. Nuclear translocation of NF-kappaB was lowered during ischemia. EGb 761 might act as direct free radical scavenger or as tocopheryl radical recycler; in both cases sparing membrane vitamin E should affect phospholipase A2 activity. Finally, EGb 761, by lowering ROS produced during ischemia, challenges nuclear translocation of NF-kappaB.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl radicals and the effects of EGb761 and its constituents.

In this study investigation is made on whether oxidative stress produced by treatment with hydroxyl radicals can induce apoptosis in rat cerebellar granule cells. The protective effects of Ginkgo biloba extract (EGb761) and its active constituents against apoptosis are also examined. The results show that hydroxyl radicals generated by the Fenton reaction induced apoptosis in cerebellar granule cells, which was associated with the decrease in the Bcl-2 mRNA level and the increase in the protein levels of the transcription factors Fos and Jun. Moreover, hydroxyl radicals induced time-dependent lipid peroxidation in cells and caused the changes in the sulfhydryl group binding sites on the membrane proteins. Hydroxyl radicals may induce apoptosis via different signaling pathways. EGb761 attenuated these changes and its different constituents showed different effects. The total flavonoid component of EGb761 and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard.

Animals↗
PubMed2006

The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats.

It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used to study the effects of repeated daily administration of EGb 761, a standardized extract from G. biloba leaves, on hippocampal-dependent spatial learning and memory and synaptic plasticity of aged rats. The adult subjects perform the Morris water maze task better than aged rats, as a cellular mechanism, the hippocampal long-term potentiation (LTP) elicited from adult animals is robust (139.29+/-2.7%). In addition, the spatial learning and memory of aged rats that had been fed on an EGb 761-supplemented diet (60 mg kg(-1)) for 30 days were significantly better than those of control aged rats. The magnitude of LTP (116.63+/-3.6%) recorded in vivo from the hippocampus CA1 area of aged rats was significantly enhanced by EGb 761 (60 mg kg(-1)). In conclusion, the spatial learning and memory of aged rats is worse than that of young subjects, and EGb 761, acting as a 'cognitive enhancer', has benefit on synaptic plasticity and cognition in aged rats. The present data further confirmed that enhancement of synaptic plasticity of the hippocampus might ameliorate the deficit in spatial learning and memory in aged rats.

Aging↗
PubMed1999

EGb 761 protects liver mitochondria against injury induced by in vitro anoxia/reoxygenation.

The present study investigated the protective effects of Ginkgo biloba extract (EGb 761) on rat liver mitochondrial damage induced by in vitro anoxia/reoxygenation. Anoxia/reoxygenation was known to impair respiratory activities and mitochondrial oxidative phosphorylation efficiency. ADP/O (2.57 +/- 0.11) decreased after anoxia/reoxygenation (1.75 +/- 0.09, p < .01), as well as state 3 and uncoupled respiration (-20%, p < .01), but state 4 respiration increased (p < .01). EGb 761 (50-200 microg/ml) had no effect on mitochondrial functions before anoxia, but had a specific dose-dependent protective effect after anoxia/reoxygenation. When mitochondria were incubated with 200 microg/ml EGb 761, they showed an increase in ADP/O (2.09 +/- 0.14, p < .05) and a decrease in state 4 respiration (-22%) after anoxia/reoxygenation. In EPR spin-trapping measurement, EGb 761 decreased the EPR signal of superoxide anion produced during reoxygenation. In conclusion, EGb 761 specially protects mitochondrial ATP synthesis against anoxia/reoxygenation injury by scavenging the superoxide anion generated by mitochondria.

Adenosine Triphosphate↗
PubMed1998

The effect of Ginkgo biloba on the activity of catalase and lipid peroxidation in experimental strangulation ileus.

This study was designed to assess the therapeutic effect of Ginkgo biloba extract (EGb 761) in experimental strangulation ileus. Rats were divided into control (n = 7), placebo (n = 11), and EGb-treated (n = 11) groups. No surgical procedure was carried out on the control group. Strangulation ileus was produced in the placebo and EGb groups for 2.5 h. At the end of this period, 100 mg/kg EGb in 1 ml of saline was injected intraperitoneally to the EGb-treated group. In the placebo group, animals received an equivalent amount of saline intraperitoneally; 24 h later, repeat laparotomies were performed to take blood and intestinal tissue samples. The EGb treatment decreased tissue malondialdehyde levels and increased catalase activities compared with the placebo group (P < 0.05 for both). Serum creatine kinase and phosphorus levels were also determined in all groups. In the placebo group these were significantly higher than in the control group (P < 0.01 and P < 0.05, respectively). In the EGb group these were not different from controls and the increase in creatine kinase activity in the EGb group was not as high as in the placebo group (P < 0.05). Our results suggest that EGb could be preventive against the effects of strangulation ileus in a rat model.

Animals↗
PubMed1996

Ginkgo biloba attenuates oxidative stress in macrophages and endothelial cells.

The action of Ginkgo biloba extract (GBE) as an antioxidant was studied using various models of oxidative stress in macrophages and vascular endothelial cells. GBE was incubated with murine macrophages (J774) at 37 degrees C and 5% CO2 for 1 h; oxidative burst was triggered by zymosan. The intensity of fluorescence was measured directly in 96-well plates using a computerized microplate fluorometer at 485 nm excitation and 530 nm emission. GBE exhibited both time- and concentration-dependent suppression of oxidative burst. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of GBE for 16 h, washed, and then exposed to an organic oxidant tert-butyl hydroperoxide (tBHP) for 2 h. Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Cell injury was assessed by measuring the release of intracellular lactate dehydrogenase (LDH), and cell viability was determined by the methylthiazol tetrazolium (MTT) assay. tBHP increased production of TBARS in PAEC. Preincubation with GBE inhibited the increase of TBARS induced by tBHP. GBE protected biomembranes from oxidative injury by decreasing intracellular LDH leakage from PAEC. MTT assay showed that GBE minimized loss of cell viability induced by oxidative injury. The extensive antioxidant effect of GBE may be valuable to the prevention and treatment of various disorders related to free radical-induced pathology.

Animals↗