Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer's Disease Patients.

BACKGROUND: One of the main features of Alzheimer's disease (AD) pathology is failure in innate immune response and chronic inflammation. Lack of effective AD treatment means that more attention is paid to alternative therapy and drugs of natural origin, such as extract of Ginkgo biloba (EGb). The purpose of this study was to investigate the effect of EGb on the mechanisms of innate immune response of peripheral blood leukocytes (PBLs) in AD patients. METHODS: In AD patients and healthy-age matched controls, the effect of EGb on two of innate immune reactions, i.e., PBLs resistance to viral infection ex vivo and production of cytokines, namely TNF-α, IFN-γ, IL-1ß, IL-10, IL-15, and IFN-α, were investigated. The influence of EGb on inflammatory-associated genes expression that regulate innate immune response to viral infection and cytokine production, namely IRF-3, IRF-7, tetherin, SOCS1, SOCS3, NFKB1, p65, and MxA was also examined. RESULTS: A beneficial effect of EGb especially in AD women was observed. EGb decreased production of TNF-α, IFN-γ, and IL-10 and increased IL-15 and IL-1ß. The effect was more pronouncement in AD group. EGb also downregulated expression of investigated genes. CONCLUSIONS: EGb may have an advantageous properties for health management in elderly and AD sufferers but especially in women with AD. Improving peripheral innate immune cells' activity by adding EGb as accompanying treatment in AD may be, in the long term, a good course to modify the disease progression.

Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm.

Alzheimer's disease (AD) represents a particular therapeutic challenge because its aetiology is very complex, with dynamic progression from preclinical to clinical stages. Several potential therapeutic targets and strategies were tested for AD, in over 2000 clinical trials, but no disease-modifying therapy exists. This failure indicates that AD, as a multifactorial disease, may require multi-targeted approaches and the delivery of therapeutic molecules to the right place and at the right disease stage. Opportunities to meet the challenges of AD therapy appear to come from recent progress in knowledge and methodological advances in the design, synthesis, and targeting of brain mRNA and microRNA with synthetic antisense oligonucleotides (ASOs). Several types of ASOs allow the utilisation of different mechanisms of posttranscriptional regulation and offer enhanced effects over alternative therapeutics. This article reviews ASO-based approaches and targets in preclinical and clinical trials for AD, and presents the future perspective on ASO therapies for AD.

Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of Ginkgo biloba (EGb) and Its Phytochemical Constituents.

Despite the availability of several anti-herpesviral agents, it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection. Extract of Ginkgo biloba (EGb) is a common phytotherapeutics around the world with health benefits. Limited studies, however, have addressed the potential antiviral activities of EGb, including herpesviruses such as Human alphaherpesvirus 1 (HHV-1) and Human alphaherpesvirus 2 (HHV-2). We evaluated the antiviral activity of EGb and its phytochemical constituents: flavonoids and terpenes against HHV-1 and HHV-2. Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity. The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations. In this work, through a comprehensive anti-HHV-1 and anti-HHV-2 activity study, it was revealed that flavonoids, especially isorhamnetin, are responsible for the antiviral activity of EGb. Such activity was absent in quercetin and kaempferol. However, EGb showed the most potent antiviral potency compared to isorhamnetin. EGb could augment current therapies for herpes labialis and genital herpes. Moreover, the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered.

Diet and Alzheimer's dementia - Nutritional approach to modulate inflammation.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease causing dementia in the elderly population. Due to the fact that there is still no cure for Alzheimer's dementia and available treatment strategies bring only symptomatic benefits, there is a pressing demand for other effective strategies such as diet. Since the inflammation hypothesis gained considerable significance in the AD pathogenesis, elucidating the modulatory role of dietary factors on inflammation may help to prevent, delay the onset and slow the progression of AD. Current evidence clearly shows that synergistic action of combined supplementation and complex dietary patterns provides stronger benefits than any single component considered separately. Recent studies reveal the growing importance of novel factors such as dietary advanced glycation end products (d-AGE), gut microbiota, butyrate and vitamin D3 on inflammatory processes in AD. CONCLUSION: This paper summarizes the available evidence of pro- and anti-inflammatory activity of some dietary components including fatty acids, vitamins, flavonoids, polyphenols, probiotics and d-AGE, and their potential for AD prevention and treatment.

The medical perspective on burnout.

OBJECTIVE: The aim of this study was to review recent medical findings related to burnout, its diagnosis, treatment, characteristic pathophysiological features, and preventive measures. MATERIALS AND METHODS: A systematic review of the scientific literature in PubMed/Medline was performed. The most recent and important findings were reported. RESULTS: Burnout was found to be a risk factor for myocardial infarction and coronary heart disease. It was also related to reduced fibrinolytic capacity, decreased capacity to cope with stress and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity. Severe burnout symptoms are associated with a lower level or smaller increase of the cortisol awakening response (CAR), higher dehydroepiandrosterone-sulphate (DHEAS) levels, lower cortisol/DHEAS ratios and stronger suppression as measured by the dexamethasone suppression test (DST). More and more literature works suggest that the evaluation of the HPA axis should be brought to the attention of primary care physicians. There is no universal agreement on specific treatment and diagnostic measures to evaluate the wide range of HPA axis disorders. The cost-effective evaluation of adrenal hormones via saliva samples by a primary care physician may significantly alter the course of therapy in numerous chronic disease patients. Psychiatric disorders may have similar symptoms, but they have distinctive hormonal profiles. Having burnout recognized as a medical condition would help in differentiating burnout from similar clinical syndromes, such as depression or anxiety, and provide appropriate treatment to burnout patients. Proper treatment is essential for a fast and full recovery. CONCLUSION: Chronic stress-related disorders often fall outside the category of a "true" disease and are often treated as depression or not treated at all. The evaluation of adrenal hormones via saliva samples helps to predict burnout. Burnout screening techniques, dietary and nutritional guidelines and lifestyle changes for supporting the HPA function need to be developed. The presented material includes hormonal, dietary, and pharmaceutical perspectives.

Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?

Flavonoids are natural, plant-derived compounds which exert diverse biological activities, also valuable neuroprotective actions within the brain and currently are intensively studied as agents able to modulate neuronal function and to prevent age-related neurodegeneration. Among them, flavones isolated from Scutellaria baicalensis root exhibit strong neuroprotective effects on the brain and are not toxic in the broad range of tested doses. Their neuroprotective potential has been shown in both oxidative stress-induced and amyloid-beta and alpha-synuclein-induced neuronal death models. Baicalein, the main flavone present in Scutellaria baicalensis root, strongly inhibited aggregation of neuronal amyloidogenic proteins in vitro and induces dissolution of amyloid deposits. It exerts strong antioxidative and anti-inflammatory activities and also exhibits anti-convulsive, anxiolytic, and mild sedative actions. Importantly, baicalein, and also another flavone: oroxylin A, markedly enhanced cognitive and mnestic functions in animal models of aging brains and neurodegeneration. In the preliminary study, wogonin, another flavone from Scutellaria baicalensis root, has been shown to stimulate brain tissue regeneration, inducing differentiation of neuronal precursor cells. This concise review provides the main examples of neuroprotective activities of the flavones and reveals their potential in prevention and therapyof neurodegenerative diseases.

The influence of donepezil and EGb 761 on the innate immunity of human leukocytes: effect on the NF-κB system.

Ginkgo biloba special extract EGb 761 and donepezil are drugs used in Alzheimer therapy. The influence of donepezil and EGb 761 on two mechanisms of innate immunity, natural antiviral resistance of human leukocytes ex vivo and NF-κB activation, was studied. Correlation between the innate immunity of leukocytes and NF-κB activation was investigated. The effect of the two drugs on resistance of human leukocytes to vesicular stomatitis virus (VSV) infection was also assessed. Two groups of healthy blood donors (n=30) were distinguished: one with resistant leukocytes (n=15) and one (n=15) with leukocytes sensitive to VSV. The degree of natural resistance of human peripheral blood leukocytes (PBLs) was determined by studying the kinetics of VSV replication. NF-κB activation was assayed by immunocytochemical staining. Efficiency of donepezil and EGb 761 was determined by a special regression model. The toxicity of the preparations to PBLs and the cell lines L(929) and A(549) and their effect on the different viruses was established. Results showed that donepezil used in concentrations of 10-50 µg/ml and EGb761 of 25-100 µg/ml stimulated resistance of human leukocytes. At the same concentrations both preparations decreased activation of transcriptional factor NF-κB. Correlation between innate immunity of PBLs and NF-κB activation was observed. Comparison of the effects of these two drugs showed that EGb 761 is more effective in stimulating leukocyte resistance. Donepezil and EGb 761 regulated innate immunity of human leukocytes by stimulating resistance and modulating NF-κB activation. The natural drug was more efficient in stimulating innate antiviral immunity of human leukocytes.

Does perfusion CT enable differentiating Alzheimer's disease from vascular dementia and mixed dementia? A preliminary report.

UNLABELLED: The purpose of the study was to evaluate the usefulness of perfusion CT (pCT) in differentiating Alzheimer's disease (AD) from vascular dementia (VaD) and mixed dementia (MixD). pCT was performed in 41 patients (mean age, 68.3 years): 24 with AD, 8 with VaD, and 9 with MixD. Regional perfusion parameters (rCBF, rCBV, and rMTT) were calculated from 31 ROIs in the grey and white matter of the frontal and temporal lobes, basal ganglia, and internal capsules bilaterally. The obtained data for the subgroups of AD, VaD, and MixD patients were compared statistically. CONCLUSIONS: On the basis of rCBF and rCBV values, pCT may be a valuable method of distinguishing between AD and VaD but it seems to be of little significance in differentiating MixD from VaD and of no usefulness in distinguishing between AD and MixD.

Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term study of its efficacy in Alzheimer's disease.

BACKGROUND: Colostrinin, a proline-rich polypeptide complex (PRP) isolated from ovine colostrum, with immunoregulatory and procognitive properties, has shown positive effects in the treatment of Alzheimer's disease (AD). The aim of the present study was to evaluate the effects of long-term Colostrinin treatment of AD patients. MATERIAL/METHODS: The patients were taking Colostrinin tablets (containing 100 mg of PRP complex) every other day for three weeks, followed by a 2-week hiatus to avoid the development of hyporeactivity. This mode of application, '3+2 weeks,' was used consistently throughout the trial. The efficacy of treatment was assessed by the MMSE scale, and each patient was evaluated at 4-month intervals. 33 patients were treated for 16 months. However, 13 patients from this group had already been treated with Colostrinin for 12 months during placebo-controlled studies, and thus participated in the trial for a total of 28 months. RESULTS: The results we obtained showed that Colostrinin induced slight but statistically significant improvement or stabilization of the health status of the patients in the trial. The adverse reactions observed, if any, were remarkably mild, including anxiety, logorrhea, and insomnia, and subsided spontaneously within a short period of time (3-4 days). CONCLUSIONS: Colostrinin is a very promising preparation which can be used to retard the development of AD.