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Approach to novel functional foods for stress control 5. Antioxidant activity profiles of antidepressant herbs and their active components.

Oxidative stress is frequently mentioned in relation to the neurodegenerative diseases. This study examined the effect of three herb extracts, Hypericum perforatum, Ginkgo biloba L. and Apocynum venetum L., and their components on lipid hydroperoxide-induced oxidative stress in PC-12 cells. Among them, the extract of Apocynum venetum and its components showed the remarkable inhibitory effect, indicating that this herb extract serves as a protective agent against lipid peroxidation-related oxidative stress in CNS. Oxidative stress may be associated with the progress of depression, as this extract has been proposed to be an effective antidepresant herb.

Animals↗

Ginkgo biloba for cognitive impairment and dementia.

BACKGROUND: Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have long been used in China as a traditional medicine for various disorders of health. A standardized extract is widely prescribed in Germany and France for the treatment of a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache. The mechanisms of action are thought to reflect the action of several components of the extract and include increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals. OBJECTIVES: The aim of the review is to assess the efficacy and safety of Ginkgo biloba for the treatment of patients with dementia or cognitive decline. SEARCH STRATEGY: Trials were identified on 26 June 2002 through a search of the CDCIG Specialized Register which contains records from all main medical databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE,LILACS), from ongoing trials databases such as Clinicaltrials.gov and Current Controlled Trials and many other sources. The search terms used were ginkgo*, tanakan, EGB-761, EGB761 and "EGB 761". SELECTION CRITERIA: All relevant, unconfounded, randomized, double-blind controlled studies, in which extracts of Ginkgo biloba at any strength and over any period were compared with placebo for their effects on people with acquired cognitive impairment, including dementia, of any degree of severity. DATA COLLECTION AND ANALYSIS: Data for the meta-analyses are based on reported summary statistics for each study. For the intention-to-treat analyses we sought data for each outcome measure on every patient randomized, irrespective of compliance. For the analyses of completers we sought data on every patient who completed the study on treatment. For continuous or ordinal variables, such as psychometric test scores, clinical global impression scales, and quality of life scales, there are two possible approaches. If ordinal scale data appear to be approximately normally distributed, or if the analyses reported by the investigators suggest that parametric methods and a normal approximation are appropriate, then the outcome measures will be treated as continuous variables. The second approach, which may not exclude the first, is to concatenate the data into two categories which best represent the contrasting states of interest, and to treat the outcome measure as binary. For binary outcomes, the endpoint itself is of interest and the Peto method of the typical odds ratio is used. MAIN RESULTS: Overall, there are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. Most studies report the analyses of data from participants who completed the treatment, there are few attempts at ITT analyses. Therefore we report completers analyses only. The CGI scale, measuring clinical global improvement as assessed by the physician, was dichotomized between participants who showed improvement and those who were unchanged or worse. There are benefits associated with Ginkgo (dose less than 200mg/day) compared with placebo at less than 12 weeks (54/63 showed improvement compared with 20/63, OR 15.32, 95% CI 5.90 to 39.80, P=<.0001), and Ginkgo (dose greater than 200mg/day) at 24 weeks (57/79 compared with 42/77, OR 2.16, 95% CI 1.11 to 4.20, P=.02). Cognition shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -0.57, 95% CI -1.09, -0.05, P=0.03, random effects model), Ginkgo (greater than 200 mg/day) at 12 weeks (SMD -0.56, 95% CI -1.12 to -0.0, P=0.05), at 12 weeks (Ginkgo any dose) (SMD -0.71, 95% CI -1.23 to -0.19 P=0.008, random effects model) at 24 weeks (Ginkgo any dose) (SMD -0.17, 95% CI -0.32 to -0.02 P=0.03) and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Activities of Daily Living (ADL) shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=0mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=<.01), Ginkgo (dose less than 200 mg/day ) at 24 weeks (SMD -0.25, 95% CI -0.49 to -0.00, P=.05), and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Measures of mood and emotional function show benefit for Ginkgo (dose less than 200 mg/day) compared with placebo at less than 12 weeks (SMD -0.51, 95% CI -0.99 to -0.03, P=.04) and Ginkgo (dose less than 200mg/day) at 12 weeks (SMD -1.94, 95% CIs -2.73, -1.15 P=<.0001). There are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. There are no data available on Quality of Life, measures of depression or dependency. REVIEWER'S CONCLUSIONS: Ginkgo biloba appears to be safe in use with no excess side effects compared with placebo. Many of the early trials used unsatisfactory methods, were small, and we cannot exclude publication bias. Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. However, the three more modern trials show inconsistent results. Our view is that there is need for a large trial using modern methodology and permitting an intention-to-treat analysis to provide robust estimates of the size and mechanism of any treatment effects.

Cognition Disorders↗

[Phytotherapeutic drugs and sleep].

Most of the studies about phythotherapeutics and sleep confirmed only hypnotic effects on subjective sleep variables. For LI 160, a hypericum extract, an induction of slow wave sleep was demonstrated in older volunteers. In patients with major depression (MD) an increase of slow wave sleep was observed by our group after a six week therapy with hypericum extract (LI 160) and after an adjunct therapy with Ginkgo biloba LI 1370 extract. In MD sleep disturbances and hypersecretion of glucocorticoids are common features. For LI 160 beneficial effects on depressed mood and for LI 1370 effects on cognitive functioning are well documented. The potential relationship between influence on sleep structure and the hypothalamic-pituitary-adrenal axis will be discussed within the neurophysiological-neuroendocrine "extended two process model" of sleep regulation.

Ginkgo biloba↗

[Ginkgo--myth and reality].

Ginkgo biloba is one of the oldest, still existing plants. Extracts from its leaves were already used in ancient China whereas in the Western World, they have been utilized only since the Sixties when it became technically possible and feasible to isolate the essential substances of Ginkgo biloba. Pharmacologically, there are two groups of substances which are of some significance: the flavonoids, effective as oxygen-free radical scavengers, and the terpenes (i.e. the ginkgolides) with their highly specific action as platelet activating factor (PAF) inhibitors. Clinically important indications for Ginkgo biloba extracts are cerebral insufficiency and atherosclerotic disease of peripheral arteries of intermediate severity. In several placebo-controlled clinical studies, symptoms of cerebral insufficiency have been effectively and significantly influenced. Most of these investigations have examined the efficacy of Ginkgo biloba extracts such as EGb 761 and LI 1370.

Arteriosclerosis↗

Ginkgo biloba and neurodegenerative disorders.

The Gingko biloba extract EGb 761 has been the subject of many studies which confirm its usefulness for the prevention and treatment of neurodegenerative pathologies. These studies have focused on: a) the probable mechanisms of action that are involved in these disorders (including non-specific mechanisms implicated in diverse neurodegenerative disorders, particularly oxidative stress, or specific mechanisms such as those associated with beta-amyloid in Alzheimer's disease) and the processes of neuronal death; b) available animal models, and c) healthy individuals or those suffering from mild cognitive impairment or Alzheimer's disease. This data must be completed, particularly with regard to new knowledge about the pathogenesis of these disorders. Ambitious interventional studies are underway and may provide new evidence regarding the effect of EGb 761 in preventing Alzheimer's disease in humans. Positive findings would be particularly interesting since this drug is very safe to use.

Aging↗

[Treatment of hemorrhoids from the viewpoint of the gastroenterologist. Personal experience with the Ginkor Fort preparation].

Pathological changes in hemorhoid plexes are frequently occurring mainly in elderly. In development of this disease are mainly involved changes in the vessel wall, pressure changes in basin, disturbances in passage of stool and also infectious disease. Instead of the correction of the life-style in therapy are used locally-acting drugs whose basis are local anesthetics, spasmolytics, antiflogistics, antipruriginostics and corticoids in many combinations. The main aim of the orally administered drugs is influence of the vessel-wall tone, decrease of the capillary permeability, circulation betterment, decrease of the oedema and blockage of the inflammatory mediators. In the group of 45 patients is documented benefit in use of Gincor-fort in dose of 2 cps bid in first week and 2 cps daily in the second week of the treatment. We presume that this drug can influence all of above mentioned factors during the acute hemorrhoidal attack.

Acute Disease↗

Ginkgo biloba.

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Diterpenes↗

Production of monoclonal antibody against ginkgolic acids in Ginkgo biloba Linn.

A competitive enzyme-linked immunosorbent assay (ELISA) for ginkgolic acids (GAs) was developed using monoclonal antibody (MAb) 9F raised against 6-(13-formylheptyl) salicylic acid covalently coupled to bovine serum albumin (BSA). ELISA, at an effective measuring range of 300 ng/ml-1 microgram/ml of GA15:1, was successful in detecting GAs content in ginkgo leaves and standardized extracts due to the lack of cross-reactivity against various related compounds. The sensitive and simple immunoassay developed in this study was validated to be specific for the quantitative determination of total GAs content in ginkgo crude drugs with no interference from the sample matrix. The analytical recovery of spiked GA15:1 was 103% in a concentration range between 10 and 40 mg/g dry weight of ginkgo leaves.

Animals↗

Liquid chromatography-electrospray mass spectrometric studies of ginkgolides and bilobalide using simultaneous monitoring of proton, ammonium and sodium adducts.

A liquid chromatographic-electrospray mass spectrometric method was developed for the determination of ginkgolides and bilobalide and was applied to the analysis of commercial products of Ginkgo biloba leaf extracts. Adducts of these compounds with ammonium, proton and sodium were detected and their relative abundance depended on the electrospray fragmentor voltage. The relative standard deviation (RSD) was improved from > 17% to < 6%, when three adduct ions of (M + H)+, (M + NH4)+ and (M + Na)+ were used for quantification compared with single ion monitoring. The characteristic mass spectra of bilobalide were different from those of ginkgolides; in particular, dimers of (2M + Na)+ were observed for bilobalide only. Analysis of 26 commercial ginkgo products revealed large variations in the composition and concentrations of ginkgolides and bilobalide in herbal products.

Chromatography, Liquid↗

Increasing trends in elderly persons' use of nonvitamin, nonmineral dietary supplements and concurrent use of medications.

OBJECTIVE: Use of nonvitamin, nonmineral dietary supplements among an elderly cohort was surveyed to determine which were the most frequently used, and to report potential medication/supplement interactions observed. DESIGN: A retrospective review of the use of 22 supplements and prescription/over-the-counter medications was collected annually from 1994 to 1999. SUBJECTS/SETTING: Supplement and medication records for an average of 359 male (36%) and female (64%) participants aged 60 to 99 years were reviewed annually. Ethnic distribution was 91% non-Hispanic white, 7% Hispanic, 1% Asian, and 1% African American. STATISTICAL ANALYSES PERFORMED: Descriptive statistics generated included mean, standard deviation, and frequency by percentage. To compare supplement user and nonsupplement user percentages across age groups, the chi 2 test was used. Linear regression was performed to test for longitudinal usage trends of each individual supplement. RESULTS: By 1999, glucosamine emerged as the most frequently used nonvitamin, nonmineral supplement followed by ginkgo biloba, chondroitin, and garlic. For women, there was a significant linear trend ( P < .05) over time for these 12 supplements: black cohosh, borage, evening primrose, flaxseed oil, chondroitin, dehydroepiandrosterone, garlic, ginkgo biloba, glucosamine, grapeseed extract, hawthorn, and St John's wort. For men, three supplements (alpha lipoic acid, ginkgo biloba, and grape-seed extract) showed a significant linear trend ( P <.05). Potential interactions between supplements and medications were seen for 10 of the 22 supplements surveyed, with a total of 142 potential interactions observed over the 6-year period. CONCLUSIONS: Examining nonvitamin, nonmineral supplement use in combination with prescription/over-the-counter medications in elderly persons is important to identify the potential risks of interactions.

Aged↗