Article

Ginkgo biloba extract improves coronary blood flow in healthy elderly adults: Role of endothelium-dependent vasodilation

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Abstract

Advancing age decreases endothelial function; accordingly, it alters the physiological regulation of coronary blood flow. Ginkgo biloba extract (GBE) has well-documented anti-ageing effects. However, little is yet known about the pharmacological actions of GBE on endothelial dysfunction and coronary blood flow in healthy elderly adults. We designed the study to test the effects of GBE on distal left anterior descending coronary artery (LAD) blood flow and endothelium-dependent brachial artery flow-mediated dilation (FMD) in healthy elderly adults. Sixty healthy elderly adults were randomly assigned to either GBE or control groups. LAD blood flow and brachial artery FMD were measured non-invasively using high-resolution ultrasound before and after intravenous administration of GBE or saline. GBE significantly increased LAD blood flow in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with the placebo group (19.16+/-13.91% vs. 0.30+/-2.55%, 17.76+/-14.56% vs. 0.53+/-2.32%, and 21.73+/-16.13% vs. 0.81+/-2.33%, MDPV, MSPV, and DTVI improvement from baseline, respectively, p<0.01). Brachial artery FMD was also increased by 56.03% (from 7.21+/-2.52% to 11.28+/-3.95%, p<0.01). A linear correlation was found between the percentage change in MDPV, MSPV, or DTVI of LAD blood flow and the percentage change in brachial artery FMD following treatment with GBE (r=0.538, 0.366, or 0.573, respectively, p<0.01, p<0.05, or p<0.01). Our data demonstrate that GBE treatment in healthy elderly adults leads to the increase of LAD blood flow in MDPV, MSPV and DTVI, and the increased response might relate to the improved endothelium-dependent vasodilatory capacity. This study implies an important future therapeutic strategy of using GBE to counteract the detrimental effects of ageing.

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... The extracts of Ginkgo biloba or its preparation, which is used extensively in at least 130 countries with $5 billion worldwide sales per year, possess antioxidant, anti-ischemia, cardiovascular and cerebrovascular activities (1)(2)(3)(4). Numerous studies and relevent regulations or guidelines had been reported to detect the total contents of flavone glycosides and terpene lactones which were much inadequate to represent their real therapeutic effect (5)(6)(7). Because the quality of herbal medicines is closely linked to the chemical components and their contents, which vary to certain extend due to different climates, cultivation conditions, harvest time, drying and storage. ...
... Fingerprint frequency ρ ρ is termed as the number of peak points obtained in unit wavenumber, seen in Eq. [2], which usually is within (0.5, 2). ...
Article
This paper aims to establish the infrared spectrum fingerprint (IRFP) in the absorbing region of 4,000-400 cm(-1) and its first derivative infrared spectrum fingerprints (d-IRFP) of ginkgo tablet (GT). And set up theories of the digitized and quantified evaluating method for super information characteristics by IRFPs of traditional Chinese medicine (TCM) which consists of the IRFP index, information index, fluctuation index, information fluctuation index and the quantified infrared fingerprint method (QIFM). Direct tabletting method was applied during the data collection of the IRFPs of 14 batches of GTs by Fourier transform infrared spectrometer. In terms of the digitized features, QIFM and similarity analysis of d-IRFP, sample S4 and S7 were evaluated as suspected outliers while the qualities of S1, S2, S6 and S12 were less well and the rests were relatively good. The assessing approach makes the expression and processing of superposed information in IRFP of TCM digitized simple and effective. What's more, an approach which can test total chemical contents in the complex system of TCM rapidly, simply and accurately was achieved by the application of QIFM based on IR technique. Finally, the quantitative and digitized infrared fingerprinting method was established as a novel approach to evaluate the quality of TCM.
... In this paper, the evaluating method of the Super Information Cluster of Ultraviolet Spectrum Fingerprints was further developed according to the theories of UVFP Index, Information Index, Fluctuation Index, Information Fluctuation Index and quantified Ultraviolet fingerprint Fingerprint Analysis of TCM Study on the digitized and quantified evaluating method for the super information cluster of traditional Chinese medicine ultraviolet spectral fingerprints method (QUFM). GTs, the most popular herbal drug (HD) used extensively in at least 130 countries with $5 billion worldwide sales per year (5), can increase peripheral and cerebral blood flow, treat dementia and decrease mental vitality at old age, tinnitus, Alzheimer's disease and depression (6)(7)(8). Numerous studies had reported to detect the contents of flavone glycosides and terpene lactones which were much inadequate to represent its real therapeutic effect (9)(10)(11). Furthermore, increasing interest in chemical fingerprint especially HPLC fingerprint (HPLC-FP) analysis can be observed, however, complex data processing, longer analysis time, and pollution of organic solvent limited its utility in manufacturer's accompanying inspection. ...
... The closer to one for γ, the poorer characteristics of a profile. Likewise, the geometric arithmetic ratio δ is defined as the ratio of the geometric mean of absorbances to the arithmetic mean of absorbances, respectively, seen Eq. [7], where A and A 0 are the arithmetic mean of absorbances and geometric mean of absorbances, separately, seen Eq. [5,6] that can also reveal how uniform are the peak signals. ...
Article
The theories of ultraviolet spectral fingerprint (UVFP) index, information index, fluctuation index, information fluctuation index combined with the quantified UV fingerprint method (QUFM) had been established and put into practice in the Ginkgo Tablets (GT) quality evaluation. The flowing injection analysis (FIA) coupled with a diode array detector was applied as a novel method to obtain the UVFP in the region of 190-400 nm at which the absorption can reflect all the information of the chemical constituents contained π→π*, n→π* and n→σ* transition. The result showed that all batches were qualified (Grade ≤3) except S8 for its too high contents. It was proved that this method made the expression of superposed information in UVFP of traditional Chinese medicine (TCM) digitized and simple. What's more, an approach which can test the total chemical content with the chromophoric characteristics in the complex system of TCM rapidly, simply and accurately was achieved by the application of QUFM. In one word, it made the exploration of the general characteristic information of the molecular absorption complex TCM in the ultraviolet regions feasible and possible.
... In patients with vascular cognitive impairment of none dementia who took a Ginkgo biloba L. extract of 19.2 mg thrice daily for 3 months, together with standard antiplatelet medication, anterior cerebral artery perfusion significantly increased, as did cognitive function test scores [168]. Finally, in healthy subjects, an extract of Ginkgo biloba L. was administered intravenously (0.7 mg/min) for 120 min, during which time coronary perfusion significantly increased [169]. This vasodilator activity seems to be attributed to the potentiation of endothelium-dependent vasodilation [169], the suppressing effect on the synthesis of endothelin-1 (ET-1) [170], and vasomotion regulation. ...
... Finally, in healthy subjects, an extract of Ginkgo biloba L. was administered intravenously (0.7 mg/min) for 120 min, during which time coronary perfusion significantly increased [169]. This vasodilator activity seems to be attributed to the potentiation of endothelium-dependent vasodilation [169], the suppressing effect on the synthesis of endothelin-1 (ET-1) [170], and vasomotion regulation. ...
Article
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(1) Background: Cardiovascular disease (CVD) is a major public health concern worldwide and a key cause of morbidity and mortality in developed countries. Accumulating evidence shows that several CVD forms are characterized by significant microcirculatory dysfunction, which may both cause and be caused by macrovascular disease, often preceding clinical manifestations by several years. Therefore, interest in exploring food supplements to prevent and restore microcirculation has grown. Given the continuous need to expand the available therapeutic arsenal for CVD, the food supplements market has recently grown and is expected to continue growing. (2) Methods: We provide an authoritative up-to-date comprehensive review of the impact of food supplementation on microcirculation by analyzing the European and American legal food supplements framework and the importance of food safety/food quality in this industry. We review the main literature about food bioactive compounds with a focus on microcirculation and some main food supplements with proven benefits. (3) Results: Despite a lack of scientific evidence, diet and microcirculatory function are clearly connected. The main food supplement examples in the literature with potential beneficial effects on microcirculation are: Ruscus aculeatus, Centella asiatica, Ginkgo biloba, Salvia miltiorrhiza, Crataegus spp., Ginseng, Mangifera indica, Aesculus hipocastanum, Hamamelis virginiana, and Vitis vinifera. (4) Conclusions: Further clinical trials are necessary to better explore the effects of these food supplements, particularly on humans.
... A large number of human intervention studies have provided evidence that a variety of flavonoid-rich foods promote vascular function. In particular, there is strong evidence for the vascular effects of flavanol-rich cocoa [104,166,167], black tea [168][169][170][171], green tea [171][172][173][174][175] and Ginko Biloba [176]. Flavonoid-induced improvements in endothelium-dependent vascular function, as indicated by increases in flow mediated dilation of the brachial artery and changes in pulse wave amplitude have been recorded in healthy subjects [104,163,164,[166][167][168][169], in older individuals [176,178], in smokers [173,174,179] and in hypertensive individuals [166]. ...
... In particular, there is strong evidence for the vascular effects of flavanol-rich cocoa [104,166,167], black tea [168][169][170][171], green tea [171][172][173][174][175] and Ginko Biloba [176]. Flavonoid-induced improvements in endothelium-dependent vascular function, as indicated by increases in flow mediated dilation of the brachial artery and changes in pulse wave amplitude have been recorded in healthy subjects [104,163,164,[166][167][168][169], in older individuals [176,178], in smokers [173,174,179] and in hypertensive individuals [166]. Such changes in vascular function have been linked to alterations in circulating nitric oxide species, suggesting that these effects are mediated by flavonoid/metabolite increases in NO production [104,163]. ...
Article
A number of contributory factors have been implicated in the pathogenesis of Alzheimer’s disease. One of these factors is chronic inflammation, with the over expression of pro-inflammatory cytokines and acute phase reactants consistently observed in the post mortem brain and plasma of AD patients. Furthermore, cardiovascular risk factors, such as hypertension, impaired vascular function and elevated LDL cholesterol, also appear to be predictive of increased dementia risk. Although classically associated with cardiovascular disease risk, both vascular and immune mediators may have direct deleterious effects on the brain, which contribute to the development of vascular dementia and Alzheimer’s disease, as well as impairments in memory and neuro-cognitive function. Dietary agents previously noted for their ability to modulate these cardiovascular risk factors leading to reductions in chronic, low-grade inflammation and/or vascular dysfunction, may also possess an ability to moderate the progression of dementia. Flavonoid-rich foods such as tea, berries and cocoa have been reported to attenuate age-related deficits in memory and cognition, although the precise mechanisms of their action are unclear. As these flavonoid rich-foods/beverages also appear to mediate inflammatory processes, attenuate endothelial dysfunction and reduce hypertension, such actions may contribute to their efficacy in the brain. This review will explore these concepts with the view to further unravelling the actions of flavonoids and flavonoid-rich foods against brain disease and to highlight the importance measuring such factors in future clinical studies.
... According to Lock et al. (2005) the total worldwide mortality attributed to inadequate intake of fruits and vegetables is around 2.6 million deaths per year. Many studies have reported the potential beneficial effects of the ingestion of the standardized commercially available extract of G. biloba L. leaves known as (EGb 761) in the management of type 2 diabetes and hypertension (Braquet and Koltai, 1994;Carlson et al., 2007;Hibatallah et al., 1999;Kubota et al., 2006;Kudolo, 2001;Kudolo et al., 2005Kudolo et al., , 2002Tada et al., 2008;Wu et al., 2008;Ye et al., 2007). However there is a lack of information about the effect of seasonal changes in the health-relevant functionality of Ginkgo leaves. ...
... Yeh et al. (2006) reported that the prevalence of patients that make use of G. biloba as complementary therapy was 4% of the survey respondents with cardiovascular disease. Wu et al. (2008) reported that the Ginkgo extract improved coronary blood flow in healthy elderly adults. Fig. 8 shows the results for the seasonal changes in the ACE inhibitory activity (%) in aqueous and ethanolic extracts of leaves from different Ginkgo trees. ...
Article
Leaves from four different Ginkgo biloba L. trees (1 and 2--females; 3 and 4--males), grown at the same conditions, were collected during a period of 5 months (from June to October, 2007). Water and 12% ethanol extracts were analyzed for total phenolics content, antioxidant activity, phenolic profile, and the potential in vitro inhibitory effects on alpha-amylase, alpha-glucosidase, and Angiotensin I-Converting Enzyme (ACE) enzymes related to the management of diabetes and hypertension. The results indicated a significant difference among the trees in all functional benefits evaluated in the leaf extracts and also found important seasonal variation related to the same functional parameters. In general, the aqueous extracts had higher total phenolic content than the ethanolic extracts. Also, no correlation was found between total phenolics and antioxidant activity. In relation to the ACE inhibition, only ethanolic extracts had inhibitory activity.
... The neuroprotective capacity of ginkgo leaves should allow for the treatment and prevention of ocular pathologies such as glaucoma, DR, and ARMD [2]. The vasoregulator effects of ginkgo through the catecholaminergic system and the release of endothelial factors, and its capacity to increase microcirculation [24], are also interesting points for this propose [25]. Finally, GBEs seem safe and well tolerated, as adverse reactions to ginkgo treatment are rare and mild [26]. ...
... The literature also describes the photo-protective effect of berries [bilberry (Vaccinium myrtillus L.), cranberry (Vaccinium oxycoccos L.), blackcurrant (Ribes nigrum L.), wolfberry (Lycium barbarum L.), grapes (Vitis vinifera L.)], stigmas [such as saffron (Crocus sativus L.)], and roots and rhizomes [such as turmeric (Curcuma longa L.) and Dan Shen (Salvia miltiorrhiza Bunge) [36,48,50,[53][54][55][56][57][58][59] on age-related ocular diseases. Ginkgo has become an increasingly well-known medicinal plant worldwide, and is used to treat peripheral vascular disease and cerebral insufficiency [16,[22][23][24]. Experimental and clinical studies have revealed the potential benefits of ginkgo for a wide range of pathological conditions, including hepatoprotective, photoprotective effects, DNA repair mechanism, and antioxidant and anti-inflammatory activities [11,12,19,[60][61][62][63]. ...
Article
Like other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.
... A meta-analysis was conducted to evaluate G. biloba 211 (120-240 mg/day) effectiveness in treating cerebrovascular insufficiency [54]. All 212 of the seven studies included in the analysis were double-blind, placebo-controlled t1:12 Gastroprotective G. biloba extract EGb (25, 50, and 100 mg/kg, ig) inhibit the increase of MDA both in gastric mucosa and in serum; significantly inhibit the ethanol-induced gastric lesions in rats [42,43] t1:14 Vasodilation G. biloba extract injectable solution Treatment in healthy elderly adults leads to the increase of LAD (left anterior descending) blood flow and improved endothelium-dependent vasodilatory capacity [44] t1:15 ...
Chapter
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Ginkgo biloba is commonly known asmaidenhair tree, available as a popular herbal supplementary in Asian, European, and American countries. Extensive in vitro, in vivo, and clinical studies demonstrated and confirmed the neuroprotective effects of a commercial standard ginkgo extract formulation known as EGb-761. Terpene trilactone comprises 5–7 % in EGb-761, collectively called as ginkgolides (G-A, G-B, G-C, G-J, G-K, G-L and G-M) and bilobides. Its clinical application gained popularity in herbal medicine due to treatment of early-stage Alzheimer’s disease, cerebrovascular disorders, PAF antagonism, and vestibular disorders. In addition, ginkgolides showed potent antioxidant activities via scavenging of reactive oxygen and nitrogen species. The physiological dosage of ginkgo extracts ranges between 120 and 240 mg/day in humans, and it is readily available as an over the counter product/supplementary product. According to the recent clinical findings, EGb-761 did not confirm its effect on long-term cognitive functioning, while it showed effectiveness and enhancement in shor-term cognitive and related activities. Ginkgo is generally well tolerated, but in a high dose, it can cause gastric upset, skin allergy, and increase the risk of bleeding in patients with risk factors (anticoagulant or antiplatelet treatment, surgery, etc.). Neuropharmacology, clinical issues of safety and usage are addressed in this book chapter.
... Ginkgo biloba increases microcirculation by improving the endothelium dependent vasodilation, as shown by the study conducted by Wu et al. [19]. ...
Article
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Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma. Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress.
... This property of ginkgo allows protection against retinal ischemia-reperfusion injury [52][53][54]. Gingko extracts inhibit LDL oxidation [55,56], have a relaxing effect on vascular walls [57], increase ocular blood flow velocity in patients [58,59], reduce systemic oxidative stress in glaucoma patients [12] (Fig. 5), and slow visual field progression in normal-tension glaucoma patients [60,61]. A daily dosage of 120 mg is efficient and safe [62]. ...
Article
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The Flammer syndrome (FS) describes the phenotype of people with a predisposition for an altered reaction of the blood vessels to stimuli like coldness or emotional stress. The question whether such people should be treated is often discussed. On the one hand, most of these subjects are healthy; on the other hand, FS seems to predispose to certain eye diseases such as normal tension glaucoma or retinitis pigmentosa or systemic diseases such as multiple sclerosis or tinnitus. A compromise between doing nothing and a drug treatment is the adaption of nutrition. But what do we mean by healthy food consumption for subjects with FS? The adaption of nutrition depends on the health condition. Whereas patients with e.g. a metabolic syndrome should reduce their calorie intake, this can be counterproductive for subjects with FS, as most subjects with FS have already a low body mass index (BMI) and the lower the BMI the stronger the FS symptoms. Accordingly, while fasting is healthy e.g. for subjects with metabolic syndrome, fasting can even dangerously aggravate the vascular dysregulation, as it has been nicely demonstrated by the loss of retinal vascular regulation during fasting. To give another example, while reducing salt intake is recommended for subjects with systemic hypertensions, such a salt restriction can aggravate systemic hypotension and thereby indirectly also the vascular regulation in subjects with FS. This clearly demonstrates that such a preventive adaption of nutrition needs to be personalized.
... The unstable oxygen supply to the retina and the optic nerve caused by high IOP, blood pressure fluctuations, or disturbed autoregulation also leads to increased oxidative stress, a main contributor to glaucomatous damage [136]. Beside its antioxidant properties, GBE also shows hemorheological and vasoactive effects, promoting erythrocytes deformability, decreasing fibrinogen levels, and improving blood viscosity and viscoelasticity [168], and increases microcirculation by improving the endothelium-dependent vasodilation [169]. Consistently, clinical observation has shown that GBE was able to significantly increase diastolic and systolic velocity in the ophthalmic artery (OA) of healthy volunteers [170]. ...
Article
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Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.
... Chen et al. reported the effects of Ginkgo biloba extract on cation currents in rat ventricular myocytes [22]. Wu et al. reported that Ginkgo biloba extract improved coronary blood flow in healthy elderly adults [23]. The typical extract of ginkgo sold in the market is standardized to contain a minimum of 6% terpene lactones (TL), 24% flavone glycosides (FGL) and less than 5 ppm ginkgolic acids [24]. ...
Article
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The aim of the study was to investigate the effect of Ginkgo biloba extract 50 (GBE50), a well-known natural antioxidant, against immunity and antioxidant enzyme activities in ischemia reperfusion (IR) rats. Rats were then divided into six groups fed for 15 days with the same diet: three groups (IV, V, VI) were treated by different doses of GBE50 suspension [20, 40, or 60 mg/kg body weight by oral gavage every day at a fixed time (10.00 a.m.)] (equal to 5, 10 and 20 times, respectively, the maximum recommended human dose), and three groups (I, II, III) were untreated. At the end of the experiment, rats' hearts were subjected to 30 min of ischemia followed by 90 min of reperfusion. Results showed that IR significantly enhanced heart rate, S-T height, myocardium (myeloperoxidase) MPO activity and blood interleukin-8 (IL-8), tumor necrosis factor Alpha (TNF-a), interleukin-1β (IL-1β) levels, blood aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatinine kinase (CK) activities, reduced myocardium sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase), calcium-magnesium adenosine triphosphatase (Ca(2+)-Mg(2+)-ATPase) activities and antioxidant enzyme activities in IR group (III) compared to sham control group (II). Pretreatment of GBE50 markedly significantly reduced heart rate, S-T height, myocardium MPO activity and blood IL-8, TNF-a, IL-1β levels, blood AST, LDH, and CK activities, enhanced myocardium Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase activities and antioxidant enzyme activities in IR group (II) compared to IR group (III). The results suggested that the GBE50 may reduce the oxidative stress in the reperfused myocardium, and increased immunity and antioxidant activities in IR rats.
... • Treatment of cerebral disorders due to aging, including cognitive decline, short-term memory, age-associated dementia, multi-infarct dementia and neurosensory impairments not associated with dementia [182][183][184][185][186][187][188][189][190][191][192][193]. • Treatment of circulatory diseases including cerebral atherosclerosis, cerebral insufficiency, symptoms in Alzheimer's disease, cancer, Parkinson's disease and rheumatoid arthritis [194][195][196][197][198][199][200][201][202][203]. • Reduction allergic reactions and inflammation, e.g., asthma, bronchospam, allergic conjunctivitis,… [204]. ...
Article
Medicinal plants are gaining in popularity due to the various advantages they offer, such as fewer side-effects, better patient compliance, relatively low cost and high accessibility as well as their high acceptability due to a long history of use. There is a widespread belief among the general public that herbal preparations are "good for humans" as they are "all natural". However, the increasing use of herbal medicinal products in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be have significant public health consequences. There is little understanding or appreciation of the fact that these "all natural" preparations are actually a combination of potentially biologically active compounds already existing in marketed products in unknown quantities. Among the most popular herbal products used worldwide is Ginkgo biloba, used for the treatment of cerebral insufficiency, peripheral vascular diseases, and frequently taken for the enhancement of memory function. Although the safety of Ginkgo biloba is promising, accumulated data show evidence of significant interactions with medications, which can place individual patients at great risk. In this review, we examined the literature from 2000 to 2008 and focused on the importance of the risk of drug interactions and potential side effects when Ginkgo biloba is involved. The aim of this systematic review is to assess the clinical evidence on interactions between Ginkgo biloba and drugs.
... In addition, these polyphenolic compounds have consistently been shown to inhibit the development of atherosclerotic lesions in animal models [88][89][90][91][92]. They may exert vascular protection by improving endothelial function, inhibiting oxidative damage and cell-cell interactions within the arterial wall, lowering high blood pressure and angiogenesis [26,86,[93][94][95][96][97][98][99]. ...
Article
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To date more than 4000 compounds are recognized to belong to the class of flavonoids. These natural phenolic drugs are poorly soluble in water and are rapidly degraded and metabolized in the human body, but nevertheless are very promising for their potential contribution to the prevention and therapy of major chronic diseases, including cardiovascular and neurodegenerative diseases and cancer. In recent years a number of flavanols (e.g. catechins), flavonols (e.g. quercetin, myricetin) and isoflavones (e.g. genistein, daidzein) have been confirmed to possess strong antioxidant, anti-inflammatory, anti-proliferative and anti-aging activities. Incorporation into lipidic or polymer-based nanoparticles appears to markedly help the oral delivery of flavonoids, as these particles can protect the drug from degradation in the gastrointestinal tract and, by virtue of their unique absorption mechanism through the lymphatic system, also from first-pass metabolism in the liver. In addition, both oral and parenteral administration of flavonoids exploits a pharmacologic delivery route that guarantees sustained release of the active principle at the desired site of action. A comprehensive review of studies currently available on the in vitro and in vivo experimental administration of flavonoids by means of nanovectors may be of use as a foundation for the development of advanced delivery systems for these powerful compounds, in view of their adoption in primary and secondary disease prevention.
... 33 Flavones inhibit phosphodiesterase-5, which is a property leveraged in antihypertensive drugs, as it has a vasorelaxant effect. 28,34,35 Another major impact on vasculature occurs through the renin-angiotensin pathway, which induces vasoconstriction. GBE decreases renin release by inhibiting prostaglandin PGI2, which positively induces renin. ...
Article
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Glaucoma is a neurodegenerative eye disease that results in retinal ganglion cell loss and ultimately loss of vision. Elevated intraocular pressure (IOP) is the most common known risk factor for retinal ganglion cell damage and visual field loss, and the only modifiable risk factor proven to reduce the development and progression of glaucoma. This has greatly influenced our approach and assessment in terms of diagnosis and treatment. However, as many as ≥50% of patients with progressive vision loss from primary open angle glaucoma without IOP elevation (≤22 mm Hg) have been reported in the United States and Canada; 90% in Japan and 80% in Korea. Extensive research is currently underway to identify the etiology of risk factors for glaucoma other than or in addition to elevated IOP (so-called "normal-tension" glaucoma; NTG) and use this knowledge to expand available treatment options. Currently, Food and Drug Administration-approved medications for glaucoma exclusively target elevated IOP, suggesting the need for additional approaches to treatment options beyond the current scope as the definition of glaucoma changes to encompass cellular and molecular mechanisms. This review focuses on alternative medical approaches, specifically Ginkgo Biloba extract, as a potential treatment option for normal-tension glaucoma.
... One study found GBE could decrease the level of reactive oxygen species and protect the mitochondrial membrane in cultured neuronal cells [26]. GBE was also found to have vasodilatory properties that could improve coronary and peripheral circulation [27], and rheological effects that could improve blood viscosity [28]. In addition, GBE can reduce active cells (e.g., glial cells) in low grade inflammation [29]. ...
Article
Glaucoma is the leading cause of irreversible blindness worldwide. Optimizing treatment is important to protecting vision. The current standard of therapy for glaucoma involves lowering the intraocular pressure (IOP) through medical, laser, and/or surgical therapy. Nevertheless, there are an increasing number of glaucoma patients that use alternative medicines to treat their glaucoma or supplement their traditional glaucoma management. Ginkgo biloba, bilberry, and medical marijuana are amongst the most commonly used medicinal plants by glaucoma patients. We reviewed the literature to determine the benefits, safety, and efficacy of these herbal remedies. Though ginkgo biloba and bilberry may prevent or slow down retinal ganglion cell death, there is no evidence yet to suggest that they alter the course of glaucoma. Medical marijuana has shown IOP lowering effect in some individuals, but its short duration of action, significant adverse effects, and addictive potential have rendered it an inappropriate standard therapeutic agent for glaucoma. Larger studies with longer durations that investigate the effect of herbal medicines on the course of glaucoma in comparison to the current standard of care are needed to elucidate their benefits in glaucoma treatment.
... Ginkgo biloba extract: Ginkgo biloba extract (GBE) exerted protective effects on the myocardial tissue by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of myocardial cells. It also had positive effects on vasodilation through endotheliumderived nitric oxide in patients with coronary artery disease [19,20]. The administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg GBE all significantly decreased the C max and AUC of clopidogrel. ...
Article
The incidence and mortality of coronary heart disease (CHD) continue to increase every year in China. It has become a serious public health concern, threatening people's health. The combination of herbs and drugs has become a common mode of treatment for various chronic diseases such as CHD and chronic lung disease. Clinical studies have shown that the combination of herbs and drugs can bring more clinical benefits in the treatment of CHD. However, safety issues caused by the interaction between herbs and drugs deserve attention. Recent findings indicate that many herbs and their active ingredients can affect the activities of cytochrome P450 enzyme system (CYP450s) and transporters related to drug metabolism, thus changing the metabolic process of combined drugs, leading to an increase or a decrease in plasma drug concentrations, finally increasing the uncertainty of clinical efficacy and the possibility of adverse events. This review aimed to discuss in detail the effect of herbs on CYP450s and/or transporters in the treatment of CHD and the potential herb-drugs interaction, thus providing the basis for the clinical rational combination of drugs.
... GBE has demonstrated several effects within the CNS that may enhance neuronal plasticity and neurotransmitter levels. For example, GBE effects have been reported, including, among others, protection of neuronal mitochondrial ATP synthesis in the presence of oxidative stress [48] [49], protection against oxidative damage in erythrocyte membranes [50], which consequently lowers blood viscosity and improves blood flow [51] [52] and neuroprotection through antiapoptotic activity [53] [54] [55] [56] [57]. ...
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The authors investigated whether a new ginkgo biloba (ginkgo) fresh plant extract had a positive effect on microcirculation in the skin and liver of elderly individuals, and whether the extract had antioxidative properties in vivo. In a monocentric, controlled clinical trial with 32 elderly patients, 16 patients received three 90 mg ginkgo extract tablets twice daily for 30 days, and 16 patients acted as untreated controls. On days 0, 10, 20, and 30, microcirculatory parameters were measured using intravital microscopy in combination with reflection spectrometry, and the amount of reduced glutathione in the liver. This new ginkgo fresh plant extract significantly increased the number of blood cell-perfused nodal points, the venular streaming flow, and the local hematocrit in treated participants compared to control participants and compared to values on day 0. The ginkgo preparation also increased microcirculation in the liver, and possessed antioxidative properties that resulted in significant increases in the amount of the radical scavenger glutathione in treated participants. The new ginkgo fresh plant extract increased the microcirculation significantly, and at the same time improved the radical scavenging capacity in elderly patients and was very well tolerated. This extract is an interesting adjuvant treatment option for patients suffering from impaired microcirculation and improves mechanisms which inhibit an accelerated expression of atherosclerosis.
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Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 microg/ml) for 2 h and then incubated with oxLDL (150 microg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE (P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.
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Ethnopharmacological relevance: Ginkgo biloba, which is one of the most frequently used herbal medicines, is commonly used in the management of several conditions, including memory impairment. Previously, it was reported to decrease the expression of peripheral benzodiazepine receptor and the biosynthesis of glucocorticoids, thereby regulating glucocorticoid levels. However, it is not known whether Ginkgo biloba extract regulates the function of the glucocorticoid receptor. Aim of the study: We determined whether Ginkgo biloba extract and several of its chemical constituents affect the activity of human glucocorticoid receptor (hGR). Materials and methods: A hGR-dependent reporter gene assay was conducted in HepG2 human hepatocellular carcinoma cells and hGR target gene expression assays were performed in primary cultures of human hepatocytes. Results: Multiple lots and concentrations of the extract and several of its chemical constituents (ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide) did not increase hGR activity, as assessed by a cell-based luciferase reporter gene assay. The extract did not influence the expression of hGR target genes, including tyrosine aminotransferase (hTAT), constitutive androstane receptor (hCAR), or pregnane X receptor (hPXR), in primary cultures of human hepatocytes. Moreover, hGR antagonism by mifepristone (also known as RU486) did not attenuate the extent of induction of hCAR- and hPXR-regulated target genes CYP2B6 and CYP3A4 by Ginkgo biloba extract. Conclusion: Ginkgo biloba extract, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are not activators of hGR. Furthermore, the extract does not influence the hGR-hCAR or the hGR-hPXR signaling pathway in primary cultures of human hepatocytes.
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Neurodegenerative diseases and various other chronic ailments have gradually transformed into public-health issues. Neurodegenerative disorders are a range of progressive neural abnormalities characterized by cellular dysfunctions, neuronal structure, and function loss. Among many chronic disorders, oxidative stress, inflammation, mitochondrial dysregulation, and cellular alterations in the human body are considered the most prevalent diagnostic symptoms. They have a profound impact on patients' health and wellbeing. The disease's poor curability, high healthcare costs, and lethality are the principal reasons for approaching and exploring the conventional treatment's phytotherapeutic alternatives. Ginkgo biloba (Maidenhair tree) is a well-known and widely used herbal plant in the Ginkgoaceae family. Its phytochemical constituents, Flavonoids, and terpenes, have been identified as the primary ingredients of Ginkgo biloba leaf extracts. It has been widely used due to its therapeutic properties, including its neuroprotective, anti-dementia, antioxidant, anti-inflammatory, vasoactive, anti-psychotic, anti-neoplastic, and anti-platelet activity. In recent decades, plenty of Ginkgo-derived substances has been researched and elucidated to have significant therapeutic effects in numerous disease models. This review aims to provide a thorough understanding of the botanical basis for Ginkgo biloba, its usage as herbal medicine, and its pivotal role in functional foods. Additionally, the clinical significance of Ginkgo biloba, as observed in various research works and clinical investigations, is also emphasized, facilitating a better understanding of their molecular basis and application in many chronic diseases.
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Background: Mental Health of Nurses in recent decades, attracted more attention. therefore strategies to reduce stress level is essential. Objective: Ginkgo biloba is one of thes herbs that has widely usage in complimentary medicine.With regard to the these points and consider of positive effects of Ginkgo biloba, this study aimed to assess the effect of Ginkgo biloba on nurses stress levels. Methods: This clinical trial was a double blined cross sectional study that nurses eligible to participate in the study using sampling methods were selected and Then randomly given drug or placebo to nurses. The medication and placebo was 40 mg, twice a day. After the two -week, the experimental and control group were switched. Result: In this study 62 nurses for two weeks consume ginkgo. Sum score of occupational stress questionnaire in case group after intervention was 40.15 with standard deviation 10.26. sum score of occupational stress questionnaire in control group after intervention was 34.55 with standard deviation 12. Conclusion: With regard that stress in nurses has problems such as decrease quality of care and unsatisfaction and unefficacy and fatigue and these factors lead to emotional disorder then intervention for control them is necessary. Therefore with regard that this research identify positive effect of ginkgo on stress levels and ginkgo is a part of complimentary therapy has a wildly application then we can use that for increase quality of life in nurses.
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Traditional optical sensing techniques, such as imaging and spectroscopy introduced in Chaps. 2 and 3, have limitations to acquire adequate spatial and spectral information for nondestructive evaluation of food and agricultural products. Generally, conventional imaging cannot acquire spectral information and spectroscopy measurement cannot cover large sample areas. In recent years, hyperspectral imaging has emerged as a powerful process analytical tool for nondestructive food analysis. It is an emerging platform technology that integrates conventional imaging and spectroscopy to attain both spatial and spectral information from an object. Therefore, hyperspectral imaging has the capability to rapidly and noninvasively monitor both physical and morphological characteristics and intrinsic chemical and molecular information of a food product for the purpose of quality and safety analyses and assessments. Some fundamental knowledge about hyperspectral imaging is introduced at first in this chapter, which includes the relationship between spectroscopy, imaging and chemical imaging, instruments for hyperspectral imaging, and image acquisition and processing. Two commonly used chemometric methods for obtaining useful features from hyperspectral images, principal component analysis (PCA) and independent component analysis (ICA), are discussed for dimension reduction and band selection. The reader is provided with a detailed overview of how to use chemometrics in hyperspectral data, along with a critical discussion on their respective advantages and potential pitfalls. The examples that we use for this purpose are the detection of chlorophyll in cucumber leaves, and the mapping of the total flavonoid distributions in fresh ginkgo leaves.
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The cardiovascular toxicities of breast cancer treatment are important health problems, with potential public health consequences. Integrative therapies may represent important tools for prevention in this population. This article reviews the cardiotoxicity of conventional breast cancer therapy, including chemotherapy, radiation, and hormonal therapy. Data are presented on the benefits of substances such as curcumin, melatonin, Ginkgo biloba, resveratrol, coenzyme Q10, and l-carnitine. Although clinical studies on many of these substances are limited both in size and number, preclinical studies are available for several, and this article summarizes the potential mechanisms of action. Areas for future research are also identified.
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Purpose of review: This study will review the research on the effect of ginkgo biloba extract (GBE) on patients with glaucoma. Recent findings: GBE appears to increase ocular blood flow in those with glaucoma. However, data on visual field outcomes are inconclusive. Summary: GBE has been shown to have antioxidant and vascular effects, making it potentially effective in treating glaucoma. Published data are limited but show an increase in ocular blood flow after GBE administration. Conclusive evidence is lacking regarding the effect of GBE on clinical outcomes in glaucoma patients such as visual field performance.
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Background and Aim: Learning and memory defect occurs following chronic diabetes with uncontrolled blood glucose. Ginkgo leaf extract improves brain blood flow. Also it contains antioxidant components and has shown beneficial effects in neurological diseases. In this study we investigated the effects of Ginkgo leaf extract on spatial memory impairment and hippocampal neuronal loss caused by diabetes. Material and Methods: This experimental study included 28 adult male Sparague-Dawley rats. The rats were made diabetic by injection of streptozotocin (STZ: 60 mg/kg). Ginkgo leaf extract (40 mg/kg) was administrated orally every day for two weeks and its effects on memory impairment and hippocampal tissue damage were investigated. Spatial memory was assessed in Morris water maze for four days. Then, the brains of the animals were extracted and after tissue staining hippocampal tissue damage were evaluated by neuronal count. Results: Latency to find the platform in water maze were significantly increased in STZ group compared to that in the control group (p
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Current treatment strategies for glaucoma are limited to halting disease progression and do not restore lost visual function. Intraocular pressure is the main risk factor for glaucoma, and intraocular pressure–lowering treatment remains the mainstay of glaucoma treatment, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. We review the literature to determine whether nutritional interventions intended to prevent or delay the progression of glaucoma could prove to be a valuable addition to the mainstay of glaucoma therapy. A total of 33 intervention trials were included in this review, including 21 randomized controlled trials. These suggest that flavonoids exert a beneficial effect in glaucoma, particularly in terms of improving ocular blood flow and potentially slowing progression of visual field loss. In addition, supplements containing forskolin have consistently demonstrated the capacity to reduce intraocular pressure beyond the levels achieved with traditional therapy alone; however, despite the strong theoretical rationale and initial clinical evidence for the beneficial effect of dietary supplementation as an adjunct therapy for glaucoma, the evidence is not conclusive. More and better quality research is required to evaluate the role of nutritional supplementation in glaucoma.
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Background Studies have demonstrated that women with low desire and low excitement have negative feelings regarding their physical and emotional satisfaction, as well as their happiness. In this study, we evaluate the efficacy of Libicare® - a multi-ingredient food supplement - to improve sexual function in postmenopausal women. Methods This was an exploratory, prospective, non-controlled, observational study. Postmenopausal women aged 45–65 with a risk of sexual dysfunction (Female Sexual Function Index (FSFI) < 25.83) were included during routine clinical visits and treated with 2 tablets of Libicare® daily for 2 months. Libicare® is an oral food supplement containing Trigonella foenum graecum, Turnera diffusa, Tribulus terrestris, and Ginkgo biloba dry extracts. Primary endpoint: change vs. baseline in FSFI score. Secondary endpoints: 1) changes in testosterone and serum steroid levels of free testosterone and sex hormone-binding globulin (SHBG) levels and 2) tolerability. Results A total of 29 patients (mean age: 54.69 years) were included. FSFI mean (SD) score showed a significant increase: 20.15 (4.48) vs 25.03 (6.94), baseline vs final; p = 0.0011, paired t-test. Most patients (86.2%) increased their FSFI score. All FSFI domains, except dyspareunia, showed significant increases. The highest increase was observed in the desire domain (p = 0.0004). Testosterone and SHBG levels were assessed in 21 patients. A significant increase in testosterone level was observed: 0.41 (0.26) vs. 0.50 (0.34) pg/mL, baseline vs. final; p = 0.038, Wilcoxon test. 52.4% of patients increased their testosterone levels. Finally, a significant decrease was observed in SHBG level: 85 (32.9) vs. 73 (26.8) nmol/L, baseline vs. final; p = 0.0001; paired t-test. 95.2% of patients decreased their SHBG levels. Conclusion In this pilot study, a significant improvement in sexual function and related hormone levels was observed with Libicare®. Further studies must be conducted to confirm these exciting results. Trial registration Current Controlled Trial ISRCTN12928573. Date of registration: 28/March/2019. Retrospectively registered.
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Background Aging-associated vascular dysfunction promotes cardiovascular disease. Recently, Ginkgo biloba extract (GBE) has attracted considerable attention in the prevention of aged vasculature. Method This review discusses the pathophysiological alterations in aged vasculature and the underlying mechanisms of GBE in vascular aging suppression. Results Both arterial stiffening and endothelial dysfunction are critical aging-related vascular phenotypes that result in the progression of cardiovascular disease in general population. Consistent oxidative stress and inflammatory reaction lead to vascular dysfunction. GBE ameliorates aging-related vascular dysfunction, due to its antioxidant and anti-inflammatory properties. The main effects of GBE in aged vasculature might be associated with longevity signaling pathways. GBE also attenuates the progression of vascular aging in diabetes mellitus via regulation of glucose and lipid metabolism. Conclusion GBE plays an important role in the prevention of vascular aging process. It is a promising therapeutic approach to ameliorate aging-related vascular dysfunction and cardiovascular diseases.
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Cerebral infarction occurs as a consequence of cerebral ischemia-reperfusion injury (CIRI). Ginkgo biloba leaf extract (GbE) is composed predominantly of active ingredients such as flavonoids and terpene lactones and often used to treat cerebrovascular diseases. However, the mechanisms underlying the use of this herbal extract to treat cerebrovascular-mediated damage are not known. The aim of this study was to examine the effectiveness of administration GbE to ameliorate the observed consequences of CIRI. The following parameters were measured: (1) behavioral score (2) infarct area (3) the content of serum malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and (4) interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression levels in the infarcted brain tissue. Data demonstrated that treatment with GbE to CIRI rats resulted in significant reduction in cerebral-infarcted area associated with improvement in behavioral score. GbE was found to decrease serum MDA levels concomitant with elevated activity levels of SOD and GSH-PX. Immunohistochemistry and Western blot analysis showed that GbE significantly lowered the levels of IL-6 and TNF-α in the infarcted brain tissue. Data suggest that GbE may be therapeutically effective in improving behavioral score in CIRI rats through reduction of oxidative stress and anti-inflammation in the cerebral infarction region.
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This study aims to determine whether there is a significant difference between the factors affecting motivation and demographic characteristics in the sample of healthcare professionals. Factors affecting motivation in the study were considered as "managerial factors, individual factors, work factors, and other factors". Survey method, one of the data collection techniques, was used. The questionnaires were applied to employees of a private hospital in Pendik district of Istanbul province through an internet link. Six hypotheses were determined for the research and their accuracy was tested with the Two-Way Variance (MANOVA) analysis, which is among the multivariate statistical methods. According to the findings, the factors affecting motivation differ significantly according to marital status, total year of working in the health sector, age, and occupation, but not according to gender and education level.
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Herbal drug treatment has been known for centuries as a part of traditional medicine. Nowadays, it is still considered a useful and natural way to treat several medical conditions, including mental disturbances. The most frequently treated mental conditions include mood disorders (mainly depression), anxiety disorders, somatoform disorders, age-related cognitive decline, and sometimes psychotic disorders. Some herbal formulations, such as St. John's wort, have been analyzed in clinical trials to estimate their real value. The use of other herbal medicines, such as Kava-kava, valerian, and Ginkgo biloba is discussed.
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Ginkgo biloba has been used in traditional Chinese medicine for about 5000 years. A standardized preparation, EGb 761 has been recently prepared. The pharmacologically active constituents, flavonol glycosides and the terpene lactones are standardized. The terpene lactones comprise of ginkgolides A, B, C and bilobalides. The extract scavenges excess free radicals and pretreatment with EGb 761 reduces damage by free radicals in patients undergoing coronary bypass surgery. The action of platelet activating factor is antagonized and platelet aggregation is reduced. Blood flow is increased. Release of prostacyclines and nitric oxide was shown to be stimulated. Ginkgo biloba has been found to be useful in the treatment of Alzheimer's disease and cognitive impairment. EGB 761 has shown beneficial effect in aging and mild cognitive impairment. Bilobalide has been shown to be protective against glutamate-induced excitotoxic neuronal death. Early studies indicate a potential role in age-related macular degeneration and some types of glaucoma. Anticancer action is related to antioxidant, anti-angiogenic and gene regulatory actions. Ginkgo biloba has shown overall improvement in about 65% of patients with cerebral impairment and a similar percentage suffering from peripheral vascular diseases. A recent study suggested that phytoestrogens in Ginkgo biloba may have a role as alternative hormone replacement therapy. Recent trials have not shown a beneficial effect of Ginkgo biloba in tinnitus and acute mountain sickness. Ginkgo biloba increased the bioavailability of diltiazem. The extract has been shown to protect against doxorubicin-induced cardiotoxicity and gentamicin-induced nephrotoxicity in animals. Ginkgo biloba inhibits microsomal enzymes and has a potential for drug interactions. Further studies to establish the efficacy of Ginkgo biloba are required.
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A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract with potent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid-reactive species (p < 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5-10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p < 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.
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Hemodynamic and electron spin resonance (ESR) analyses were performed on isolated ischemic and reperfused rat hearts to assess the cardioprotective and antioxidant effects of therapeutically relevant concentrations of Ginkgo biloba extract (EGb 761; 5, 50 or 200 microg/ml), its terpenoid constituents (ginkgolide A; 0.05 microg/ml and ginkgolide B; 0.05, 0.25 or 0.50 microg/ml), and a terpene-free fraction of EGb 761 (CP 205; 5 or 50 microg/ml). Hearts underwent 10 min of low-flow ischemia, 30 min of no-flow global ischemia, and 60 min of reperfusion. Test substances were added to the perfusion fluid during the last 10 min of control perfusion, low-flow ischemia and the first 10 min of reperfusion. A separate group of rats was treated with CP 205 (60 mg/kg/day; p.o.) for 15 days, after which the hearts were perfused with plain buffer. In ESR experiments, the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was added to the perfusate to determine the effects of treatments on post-ischemic myocardial free radical generation. Results showed that in vitro exposure of hearts to EGb 761 (5 or 50 microg/ml) or to ginkgolides A and B (both at 0.05 microg/ml), or in vivo pretreatment of the rats with CP 205 delayed the onset of contracture during ischemia. The strong reperfusion-induced elevation of left ventricular end-diastolic pressure observed in untreated hearts was significantly reduced by in vitro exposure to the lowest concentrations of EGb 761, by ginkgolide A, and to a lesser extent by ginkgolide B, or by prior oral treatment with CP 205. Post-ischemic functional recovery.was significantly improved by in vivo administration of CP 205, by perfusion with 5 microg/ml of EGb 761 or with both terpenoids as compared to untreated group but in vitro CP 205 was not effective. ESR analyses revealed that DMPO-OH (the DMPO/hydroxyl radical spin-adduct) concentrations in coronary effluents were markedly decreased by all treatments, except for the lowest concentration of ginkgolide B. Perfusing 5 microg/ml EGb 761 resulted in a better inhibition of baseline DMPO-OH concentration than 5 microg/ml CP 205 (-70 % and -48 % vs. control, respectively), indicating that both terpenoid and flavonoid constituents of EGb 761 are required to produce this effect. CP 205 was significantly more efficient in reducing DMPO-OH concentration when administered in vivo than when applied in vitro, indicating that the antioxidant effect of flavonoid metabolites (formed in vivo) is superior to that of intact flavonol glycosides (present in vitro). Collectively, these findings provide the first evidence that part of the cardioprotection afforded by EGb 761 is due to a specific action of its terpenoid constituents and that this effect involves a mechanism independent of direct free radical-scavenging. Thus, the terpenoid constituents of EGb 761 and the flavonoid metabolites that are formed after in vivo administration of the extract act in a complementary manner to protect against myocardial ischemia-reperfusion injury.
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Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. We investigated the relationship between coronary and peripheral endothelial function. In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.
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We previously demonstrated that Ginkgo biloba extract (GBE) produced vasodilation via the nitric oxide synthesis and release by increasing the intracellular calcium level in vascular endothelial cells of rats. The present study aimed to clarify the effects of dietary administration of GBE on the blood pressure and vascular tone of hypertensive Dahl salt-sensitive (Dahl) rats in order to evaluate its therapeutic actions and availability. Dahl rats were fed an 8.0% NaCl diet or an 8.0% NaCl plus 0.5% GBE diet for 24 d. The feeding of GBE did not change the heart rate, but significantly decreased systolic blood pressure. After 24 days' administration, the effects of GBE on the atria and aorta isolated from Dahl rats were examined. The GBE-containing diet did not affect the negative and positive actions of isolated atria that were produced by acetylcholine and isoproterenol, respectively. In the aortic preparations, the relaxation in response to acetylcholine was significantly potentiated by a GBE-containing diet. Sodium nitroprusside-induced relaxation was unchanged by GBE-containing diet. These results demonstrated that GBE reduced salt-related elevation of blood pressure and restored the impaired acetylcholine-induced vasodilation in aortic segments.
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Aging per se is associated with abnormalities of the vascular wall linked to both structural and functional changes that can take place at the level of the extracellular matrix, the vascular smooth muscle and the endothelium of blood vessels. Endothelial dysfunction is generally defined as a decrease in the capacity of the endothelium to dilate blood vessels in response to physical and chemical stimuli. It is one of the characteristic changes that occur with age, independently of other known cardiovascular risk factors. This may account in part for the increased incidence of cardiovascular events in elderly people that can be reversed by restoring endothelial function. A better understanding of the mechanisms involved and the aetiopathogenesis of this process will help in the search for new therapeutic agents. Age-dependent alteration of endothelium-dependent relaxation seems to be a widespread phenomenon both in conductance and resistance arteries from several species. In the course of aging, there is an alteration in the equilibrium between relaxing and contracting factors released by the endothelium. Hence, there is a progressive reduction in the participation of nitric oxide and endothelium-derived hyperpolarising factor associated with increased participation of oxygen-derived free radicals and cyclo-oxygenase-derived prostanoids. Also, the endothelin-1 and angiotensin II pathways may play a role in age-related endothelial dysfunction. The use of drugs acting at different levels of these signalling cascades, including antioxidant therapy, lipid-lowering drugs and estrogens, seems to be promising.
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We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)–sensitive flow-induced dilations were significantly impaired (Y: 41±8% versus A: 3±2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not l-arginine or the TXA2 receptor antagonist SQ29,548). For lucigenin chemiluminescence, O2·− generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O2·− generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O2·− (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47phox, p67phox, Mox-1, and p22phox did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations. We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)–sensitive flow-induced dilations were significantly impaired (Y: 41±8% versus A: 3±2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not l-arginine or the TXA2 receptor antagonist SQ29,548). For lucigenin chemiluminescence, O2·− generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O2·− generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O2·− (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47phox, p67phox, Mox-1, and p22phox did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.
Article
Background: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries.Hypothesis: We investigated the relationship between coronary and peripheral endothelial function.Methods: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 μg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values.Results: Flow-mediated dilation (FMD) of the brachial artery was 5.0 ± 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 μg/min, r=0.31, p<0.05) but also with the change in CBF (ACh at 3 μg/min, r=0.39, p<0.05; ACh at 30 μg/min, r=0.46, p<0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF.Conclusions: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.
Article
The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2-deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage.
Article
Spirally-cut strips of rabbit aorta were used to examine the relaxations produced by carbachol and extract of Ginkgo biloba (Gb) under isometric conditions. After precontracting the strips with phenylephrine (10(-7) M), carbachol produced a dose-related relaxation (PD2 congruent to 6.2 +/- 0.1) and this effect was antagonized competitively by atropine (PA2 congruent to 9.4 +/- 0.1). Gb (0.2 or 0.3 mg/ml) also relaxed the strips. Removal of the endothelium or a 30-min pre-treatment of the strips with a substance that has lipoxygenase-inhibitor activity (nordihydroguaiaretic acid, NDGA, 10(-5) M) abolished the relaxant effect of carbachol and partially blocked the relaxant effect of Gb. Thus, at least part of the relaxant effect of Gb is mediated by a factor(s) (e.g., EDRF) that is released from endothelial cells.
Article
This study assessed whether aging is associated with progressive endothelial dysfunction, whether the pattern of any age-related decline in vascular health is different in men and women and whether any gender difference is consistent with known changes in hormonal status. Coronary and cerebrovascular disease are much less common in young and middle-aged women compared with men, although the gender difference in death from atherosclerosis is less marked after the menopause. Endothelial dysfunction is an early event in atherogenesis and is important in dynamic plaque stenosis in later life. The effect of aging on endothelial function in men and women, however, is not well known. We used high resolution ultrasound to study endothelium-dependent and endothelium-independent vascular responses. Brachial artery physiology was investigated in 238 subjects (103 men, 135 women; mean [+/- SD] age 38 +/- 17 years, range 15 to 72) with no known risk factors for atherosclerosis. The responses to reactive hyperemia (flow-mediated dilation, which is endothelium dependent) and to glyceryl trinitrate (an endothelium-independent dilator) were assessed for all the subjects and then for men and women separately. On multivariate analysis for the whole group, reduced flow-mediated dilation was related to older age (r = -0.34, p < 0.0001). In men, flow-mediated dilation was preserved in subjects aged < or = 40 years but declined thereafter at 0.21%/year. In women, flow-mediated dilation was stable until the early 50s, after which it declined at 0.49%/year (p = 0.002 compared with men). In contrast, there was no significant change in the glyceryl trinitrate response with aging in either gender. Aging is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women. In women, however, a steep decline commences at around the time of the menopause. This is consistent with a protective effect of estrogens on the arterial wall.
Article
It has been suggested that endothelium-related vasomotion is important in the control of coronary circulation. Our goal was to determine if endothelium-dependent dilation of the coronary vasculature was altered with aging in 18 patients with atypical chest pain (age, 23-70 years) who had angiographically normal coronary arteries and no coronary risk factors. We infused an endothelium-dependent vasodilator acetylcholine (1, 3, 10, and 30 micrograms/min) and an endothelium-independent vasodilator papaverine (10 mg) into the left coronary artery. The large coronary diameter was assessed by arteriography, and the increase in coronary blood flow was measured using the intracoronary Doppler catheter technique. Acetylcholine increased coronary blood flow in a dose-dependent manner with no changes in arterial pressure and heart rate. The maximum increase in coronary blood flow evoked by acetylcholine varied widely among patients (increase in coronary blood flow ranged from 200% to 560%) and was correlated significantly with aging (r = -.86, P < .001), whereas the peak coronary blood flow response to papaverine was affected slightly by aging (r = -.44, P = .07). The percent increase in blood flow response to acetylcholine to the response to papaverine correlated with aging (r = -.87, P < .001). The slope of the coronary blood flow response to acetylcholine also correlated significantly with aging. The large epicardial coronary artery response to the low doses of acetylcholine (< or = 10 micrograms/min) correlated inversely with aging. The results of this study suggest that endothelium-dependent dilation of coronary arteries evoked by acetylcholine may be decreased with aging in humans.
Article
1. Extracts from the leaves of Ginkgo biloba (EGb) and ginsenosides (GS) have been reported to be effective at increasing vascular relaxation. In the present study, the actions of EGb and GS on the vascular functions of porcine basilar arteries were investigated in vitro using tissue bath techniques. 2. Both EGb and GS relaxed the basilar artery in a concentration-dependent and partly endothelium-dependent manner. However, EGb appeared to be more potent than GS. Relaxation induced by transmural nerve stimulation (TNS) was significantly enhanced by EGb (7.5, 15 and 30 μg/mL) and GS (20, 40 and 80 μg/mL| in both endothelium-intact and -denuded basilar arteries. Enhanced TNS-induced relaxations were abolished by 0.3 mmol/L N-h -arginine. 3. The present study demonstrates that nitric oxide plays a primary role in TNS-induced relaxation as well as in EGb- and GS-enhanced relaxation within the cerebral vasculature. In addition, our data support the potential of these compounds as therapeutic strategies in cerebral ischaemia and other related vascular dysfunctions.
Article
Endothelial dysfunction has been described with ageing but the mechanisms responsible have not been clearly elucidated and might be different from one vessel to the other. This study assesses the relative contribution of endothelial nitric oxide (NO) and cyclo-oxygenase (COX) metabolites in relaxation to acetylcholine with ageing in the aorta and the small mesenteric artery of the rat. In the aorta and branch II or III of superior mesenteric artery (SMA), endothelium-dependent relaxation to acetylcholine was not different between 12–14 (adult) and 32-week-old rats whereas it was reduced at 70–100 (old) weeks of age. Despite an increased endothelial NO-synthase protein expression, the NO-synthase inhibitor, NG-nitro-L-arginine-sensitive component of relaxation decreased with ageing. In old rats, exposure to the COX inhibitor, indomethacin, but not the selective COX-2 inhibitor, NS-398, potentiated response to acetylcholine. The thromboxane A2/prostaglandin H2 receptor antagonist, GR 32191B enhanced relaxation to acetylcholine in aorta but it had no effect in SMA. Furthermore, acetylcholine increased thromboxane B2 production (enzymeimmunoassay) in aorta but not in SMA. Finally, Western blot analysis showed enhanced expression of COX-1 and 2 in the two arteries with ageing. These results suggest that the decrease in acetylcholine-induced relaxation with ageing involves reduced NO-mediated dilatation and increased generation of vasoconstrictor prostanoids most likely from COX-1. They also point out vascular bed heterogeneity related to the nature of prostanoids involved between the aorta (i.e., thromboxane A2) and the SMA (unidentified) arteries even though increased expression of COX occurs in both vessels. British Journal of Pharmacology (2000) 131, 303–311; doi:10.1038/sj.bjp.0703568
To examine the anti-free radical related cardiovascular protective effects and NO-mediated cerebrovasorelaxant effects of extract of the leaves of Ginkgo biloba(EGb) in isolated preparations. Experiments on the anti-free radical related cardiovascular protective effects were performed in rabbit Langendorff heart and isolated aortic rings damaged by diphenyl-picryl hydyazyl(DPPH). Protective effects of EGb were determined by comparing the results of EGb pretreated group with the DPPH-injured controls. Cerebrovasorelaxant effects of EGb were examined in ring preparations of isolated porcine basilar artery in vitro using tissue bath techniques. EGb protected the isolated rabbit heart from the DPPH-injury to the cardiac contractility and the aortic endothelium from DPPH-attenuated ACh-induced relaxation. EGb concentrationde dependently relaxed the basilar artery and this effect was more significant in endothelium intact rings than those endothelium denuded rings. EGb enhanced the TNS-induced relaxation in basilar artery and this effect was abolished by pretreatment of N-nitro-L-arginine or tetrodotoxin. EGb exerts cardiovascular protection against DPPH-impaired cardiac contraction in rabbit isolated heart and endothelium-dependent relaxation in the aortic ring of rabbit in vitro. EGb relaxes porcine basilar artery and enhances the TNS-induced relaxation via a NO pathway.
Article
The effect of Ginkgo biloba (EGb), a plant extract with an antioxidant effect, has been studied on gentamicin-induced nephrotoxicity in male wistar rats. Ginkgo biloba extract (300 mg/kg BW) was administered orally 2 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Saline treated animals served as control. Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue MDA were carried out after 8 days of gentamicin treatment. Kidneys were examined using histological techniques. Blood urea and serum creatinine were increased by 896% and 461% respectively, with gentamicin, compared to saline treated group. Creatinine clearance was significantly decreased with gentamicin. Ginkgo biloba extract protected rats from gentamicin-induced nephrotoxicity. Changes in blood urea, serum creatinine and creatinine clearance induced by gentamicin were significantly prevented by Ginkgo biloba extract. There was a 177% and 374% rise in plasma and kidney tissue MDA with gentamicin, which were significantly reduced to normal with Ginkgo biloba extract. Histomorphology showed necrosis and desquamation of tubular epithelial cells in renal cortex with gentamicin, while it was normal and comparable to control with Ginkgo biloba extract. These data suggest that supplementation of Ginkgo biloba extract may be helpful to reduce gentamicin nephrotoxicity.
Article
We tested whether adenosine mediates nitric oxide (NO)-dependent and NO-independent dilation in coronary and aortic smooth muscle and whether age selectively impairs NO-dependent adenosine relaxation. Responses to adenosine and the relatively nonselective analog 5'-N-ethylcarboxamidoadenosine (NECA) were studied in coronary vessels and aortas from immature (1-2 mo), mature (3-4 mo), and moderately aged (12-18 mo) Wistar and Sprague-Dawley rats. Adenosine and NECA induced biphasic concentration-dependent coronary vasodilation, with data supporting high-sensitivity (pEC(50) = 5.2-5.8) and low-sensitivity (pEC(50) = 2.3-2.4) adenosine sites. Although sensitivity to adenosine and NECA was unaltered by age, response magnitude declined significantly. Treatment with 50 microM N(G)-nitro-L-arginine methyl ester (L-NAME) markedly inhibited the high-sensitivity site, although response magnitude still declined with age. Aortic sensitivity to adenosine declined with age (pEC(50) = 4.7 +/- 0.2, 3.5 +/- 0.2, and 2.9 +/- 0.1 in immature, mature, and moderately aged aortas, respectively), and the adenosine receptor transduction maximum also decreased (16.1 +/- 0.8, 12.9 +/- 0.7, and 9.6 +/- 0.7 mN/mm(2) in immature, mature, and moderately aged aortas, respectively). L-NAME decreased aortic sensitivity to adenosine in immature and mature tissues but was ineffective in the moderately aged aorta. Data collectively indicate that 1) adenosine mediates NO-dependent and NO-independent coronary and aortic relaxation, 2) maturation and aging reduce NO-independent and NO-dependent adenosine responses, and 3) the age-related decline in aortic response also involves a reduction in the adenosine receptor transduction maximum.
Article
Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.
Article
Compensatory enlargement of the coronary arterial wall has been described in the early stages of native atherosclerosis. However, little is known about the specific effect of aging on this adaptive process in atherosclerosis. The purpose of the current study was to characterize the effects of advancing age on vascular remodeling and endothelium-dependent and -independent coronary vasodilation in patients without coronary artery disease risk factors. Twenty-six patients without coronary risk factors and with normal and mildly diseased coronary arteries were studied. Vessel, lumen and atherosclerotic plaque areas were evaluated by intravascular ultrasound and coronary flow response was assessed using papaverine and acetylcholine in the left anterior descending coronary artery. There was a weak but significant correlation between plaque area and age (r = 0.29, P<0.01). Vessel area was also weakly but significantly correlated with age (r = 0.22, P<0.05). However, lumen area had no correlation with age. Vessel area in the younger group (<50 years) and the older group (> or =50 years) increased 1.64 and 0.55 mm2 for every 1 mm2 increase in plaque area (r = 0.62, P<0.0001 and r = 0.39, P<0.05, respectively). With regard to vascular reactivity, there was an inverse correlation between the percentage increases in coronary blood flow (CBF) evoked by acetylcholine and aging (r = -0.49, P<0.05). The percentage increases in CBF evoked by papaverine also inversely correlated with aging (r=-0.53, P<0.01). However, the percentage changes in coronary artery diameter evoked with acetylcholine did not correlate with aging. This study suggests that endothelium-dependent and -independent vasodilation of the resistance coronary artery are impaired with advancing age, which may be in association with attenuated coronary vascular remodeling with aging.
Article
It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl4) and EGb groups, and were given normal saline, CCl4 and CCl4 plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl4 group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl4 group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl4. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.
Article
To investigate the effects of total lactones of ginkgo on aging by using D-galactose induced aging mice and natural aging mice. By using D-galactose induced aging mice, to detect the LF content in heart and liver, the Hyp content in liver, the MAO, GSH-Px activities and the NO content in cerebrum. The apoptosis of cerebral cell was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling (Tunel) in natural aging mice. TLG was shown to increase the GSH-Px activities, reduce the NO content and decrease the MAO activity in cerebrum. Meanwhile, TLG was found to reduce the LF content in liver and heart and raise the Hyp content in liver. TLG was shown to inhibit apoptosis of cerebral cell and decrease the number of apoptotic cells in the brain. TLG possesses effect on antiaging via attenuating lipid peroxidation and NO and apoptosis of cerebral cells.
Article
To observe the activity of peripheral blood monocytes (PBMs) derived macrophage scavenger receptors (MSR) and changes of serum inflammatory factor in peripheral blood in patients with coronary heart disease (CHD), and to evaluate the effect of Ginkgo biloba extract (GBE) on the MSR activity, to explore the relationship between inflammatory factor and scavenger receptors activity as well as the possible mechanism of GBE in stabilizing the atheromatous plaque. Ninety-seven CHD patients with normal blood lipids were classified into the stable angina group, the unstable angina group and the acute myocardial infarction group, and 29 healthy persons were taken as control. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in all subjects were determined. And their PBMs were isolated, cultured in vitro, and transferred into macrophage to observe the effect of GBE on the expression of scavenger receptors. The levels of MSR activity, CRP, sICAM-1 and sVCAM-1 in patients with acute myocardial infarction > unstable angina > stable angina > control. GBE could down-regulate the MSR activity in CHD patients, which was positively correlated with levels of CRP, sICAM-1 and sVCAM-1. MSR activity could be taken as a monitoring criteria for active degree of vulnerable atherosclerosis plaque. GBE has the effect of suppressing MSR activity.
Article
Vasodilating actions of Ginkgo biloba extract (GBE) and bilobalide, a main constituent, were examined using rat aorta ring strips. GBE at the concentration ranges from 0.03 to 3 mg/ml had a potent concentration-dependent relaxation, reaching 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Bilobalide at 0.1 to 100 microM also caused the relaxation in a concentration-dependent manner. At 100 microM, bilobalide caused dilation by 17.6 +/- 3.9% (n = 7, P < 0.05). NG-monomethyl-L-arginine acetate (L-NMMA)(100 microM), an NO synthesis inhibitor, reduced the vasodilation of GBE (3 mg/ml) to 57.6 +/- 2.5% (n = 6, P < 0.05), and was accompanied with a decrease in the rate of relaxation. Tetraethylammonium (TEA)(100 microM), a Ca(2+)-activated K(+) channel inhibitor, also decreased the GBE (3 mg/ml)-induced relaxation to 63.1 +/- 4.6% (n = 6), but not significantly. Indomethacin tended to reduce the GBE (3 mg/ml)-induced vasorelaxation to 67.3 +/- 4.1% (n = 6). In contrast, the vasorelaxation of GBE (3 mg/ml) was strongly attenuated to 53 +/- 6.1% (n = 7, P < 0.05) in Ca(2+)-free medium. Similarly, the vasorelaxation induced by bilobalide significantly decreased both by pretreatment with NO inhibitor (L-NMMA) and in Ca(2+)-free solution. These results indicate that the relaxation induced by GBE would be due to the inhibition of Ca(2+) influx through the Ca(2+) channel and the activation of NO release, and might be in part due to the inhibitions of Ca(2+)-activated K(+) current and PGI(2) release, in the endothelium and aortic vascular muscles. Bilobalide possesses the similar mechanisms for the vasodilation.
Article
We evaluated the significance of the diastolic-to-systolic blood flow velocity ratio (DSVR) determined by transthoracic Doppler echocardiography, for a physiologic assessment of the severity of coronary stenosis without stress tests, as compared with thallium 201 single photon emission computed tomography. In 95 patients undergoing thallium 201 single photon emission computed tomography for coronary artery disease, the flow velocity in the distal left anterior descending coronary artery was obtained with transthoracic Doppler echocardiography. The mean and peak DSVR values were calculated using mean and peak coronary flow velocity. DSVR was successfully measured for 82 patients (86.3%), including 33 patients with reversible perfusion defects in the left anterior descending coronary artery territories. For predicting reversible perfusion defects in thallium 201 single photon emission computed tomography, the best cut-off points were 1.5 for mean DSVR (sensitivity 81.8%, specificity 85.7%) and 1.6 for peak DSVR (sensitivity 75.7%, specificity 83.6%). Noninvasive measurement of DSVR with transthoracic Doppler echocardiography provides physiologic estimation of the left anterior descending coronary artery stenosis severity at high success rate, without stress tests.
Article
We previously demonstrated that Ginkgo biloba extract (Ginkgo) produced vasodilation via the nitric oxide pathway in aortic segments isolated from Wistar rats. In this study, we have analysed the effects of daily long-term oral Ginkgo treatment on blood pressure, vascular tone, and calcium mobilization to evaluate the clinical availability. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were fed either a control diet or a diet containing 0.05%-0.5% Ginkgo for 30 days. Administration of Ginkgo did not change systolic blood pressure in WKY, but significantly decreased systolic blood pressure in SHR. In thoracic aortic preparations isolated from SHR, diminished relaxation in response to acetylcholine was improved by a Ginkgo-containing diet. This diet significantly decreased the EC50 value and significantly increased maximum relaxation in response to acetylcholine in SHR. In aortic segments isolated from WKY, acetylcholine-induced relaxation was not affected by a Ginkgo-containing diet. Sodium nitroprusside-induced relaxation was unchanged by a Ginkgo-containing diet in SHR and WKY. We also examined the effects of a Ginkgo-containing diet on the intracellular calcium level of aortic endothelium using a fluorescent confocal microscopic imaging system. Calcium Green 1/AM preloading indicated that acetylcholine significantly increased the endothelial intracellular calcium level. The Ginkgo-containing diet significantly enhanced this increase in the aortic endothelium of SHR, but did not change that of WKY. The results suggested that Ginkgo enhanced endothelium-dependent vasodilation and elevation of the endothelial intracellular Ca(2+) level in SHR, resulting in hypotension. This accelerative effect of Ginkgo on Ca(2+) mobilization seemed to be associated with restoration of impaired dilatory function induced by acetylcholine in endothelial cells.
Article
Aging per se is associated with abnormalities of the vascular wall linked to both structural and functional changes that can take place at the level of the extracellular matrix, the vascular smooth muscle and the endothelium of blood vessels. Endothelial dysfunction is generally defined as a decrease in the capacity of the endothelium to dilate blood vessels in response to physical and chemical stimuli. It is one of the characteristic changes that occur with age, independently of other known cardiovascular risk factors. This may account in part for the increased incidence of cardiovascular events in elderly people that can be reversed by restoring endothelial function. A better understanding of the mechanisms involved and the aetiopathogenesis of this process will help in the search for new therapeutic agents.Age-dependent alteration of endothelium-dependent relaxation seems to be a widespread phenomenon both in conductance and resistance arteries from several species. In the course of aging, there is an alteration in the equilibrium between relaxing and contracting factors released by the endothelium. Hence, there is a progressive reduction in the participation of nitric oxide and endothelium-derived hyperpolarising factor associated with increased participation of oxygen-derived free radicals and cyclo-oxygenase-derived prostanoids. Also, the endothelin-1 and angiotensin II pathways may play a role in age-related endothelial dysfunction. The use of drugs acting at different levels of these signalling cascades, including antioxidant therapy, lipid-lowering drugs and estrogens, seems to be promising.
Article
To evaluate the effects of Ginaton (Ginkgo biloba leaf extract) on the myocardial injury markers (MIMs) during cardiopulmonary bypass (CPB). Forty patients with congenital heart diseases, scheduled to take atrial septum or ventricular septum repairing operation, were randomly divided into the Ginaton group and the control group, 20 cases in each group. Patients in both groups received St. Thomas' cardioplegic perfusion via radix aortae, while Ginaton (0.5 mg/kg) was added into the perfusion for the Ginton group. Cardiac surgery were started after complete heart arrest. Central venous blood was obtained before and at 0, 6th, 12th, 24th and 48th hour after operation for detection of serum C reaction protein (CRP) by immunoturbidimetry, as well as creation kinase-MB isoenzyme (CK-MB), cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with enzyme-linked immunosorbent assay (ELISA). There was no difference in serum concentration of CRP, CK-MB, cTnT and cTnI between the two groups before operation (P > 0.05). These indexes increased immediately after operation in both groups ( P < 0.05). They reached the peak value 12 hrs after CPB and reduced to normal level 48 hrs post-operation in the control group, with the value significantly higher than that in the Ginaton group at all the corresponding time points (P < 0.05, or P < 0.01). Perfusion with Ginaton during CPB could significantly decrease the release of MIMs and improve post-CPB cardiac function recovery, exerting favorable myocardium-protective effects.
Article
Ginkgo biloba extract EGb 761 was studied for its nephroprotective effects in experimentally diabetic and hypoxic rats. Duration of streptozotocin-induced diabetes was 4 months, that of respiratoric hypoxia of the diabetic group 20 min. The daily dose of 100 mg EGb/kg bodyweight started 1 month after induction of the diabetes. EGb reduced diabetes-induced morphological alterations of the kidney such as increase in volume of glomeruli, capillary tufts, urinary space, and thickening of Bowman's capsule basement membrane. Diabetically increased immunostaining of interstitial collagenes of types I, III, and VI was diminished by the EGb extract. EGb reduced the relative total SOD activity from 163% in diabetic kidney to 46%. Additional hypoxia-induced ultrastructural damage was also diminished.
Article
Homocysteine is an independent risk factor for atherosclerosis. The objective of this study was to investigate whether ginkgolide A (GA), a major constituent of Ginkgo biloba, could block homocysteine-induced endothelial dysfunction in porcine coronary arteries. Porcine coronary artery rings were assigned to six treatment groups: control; homocysteine (50 micromol/L); low-dose (50 micromol/L) or high-dose (100 micromol/L) GA; and homocysteine plus low-dose or high-dose GA. After 24 hours' incubation, the rings were analyzed for vasomotor function in response to a thromboxane A2 analogue (U46619), bradykinin, and sodium nitroprusside. Endothelial nitric oxide synthase (eNOS) was studied by using real-time polymerase chain reaction and immunohistochemistry analysis. Superoxide anion production was assessed by chemoluminescence analysis. Endothelium-dependent relaxation (bradykinin) was significantly reduced in ring segments treated with homocysteine as compared with the control (P < .05). When homocysteine was combined with either low-dose or high-dose GA, endothelium-dependent relaxation was markedly recovered. There was no significant difference in maximal contraction (U46619) or endothelium-independent relaxation (sodium nitroprusside) among all groups. In addition, superoxide anion production was increased by 113% in the homocysteine-treated group, whereas there was no statistically significant difference between the control and GA/homocysteine groups. Furthermore, eNOS messenger RNA and protein levels were substantially reduced in the homocysteine-treated group (P < .05), but not in the GA/homocysteine combined groups. Homocysteine significantly impairs endothelium-dependent vasorelaxation through oxidative stress and downregulation of eNOS in porcine coronary arteries. GA effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores the potential clinical benefits and applications of GA in controlling homocysteine-associated vascular injury and cardiovascular disease. Homocysteine is an independent risk factor for atherosclerosis. This study showed that ginkgolide A, a major constituent of Ginkgo biloba, effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores potential clinical benefits and applications of ginkgolide A in controlling homocysteine-associated vascular injury and cardiovascular disease.
Advancing age is associated with diminished vascular remodeling and impaired vasodilation in resistance coronary arteries
  • Ishida