Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular deposits of amyloid ß peptide (Aß) and microglia-dominated neuroinflammation. The therapeutic options for AD are currently limited. In this study, we investigated the antiinflammatory effects and the underlying molecular mechanisms of Ginkgo biloba extract EGb 761 when administered to TgCRND8 AD mice, which overexpress human Alzheimer's amyloid precursor protein (APP) specifically in neurons. We gave APP-transgenic mice EGb 761 as a dietary supplement for 2 or 5months. Plasma concentrations of EGb 761 components in mice were in the same range as such concentrations in humans taking EGb 761 at the recommended dose (240mg daily). Treatment with EGb 761 for 5months significantly improved the cognitive function of the mice as measured by the Barnes Maze test. It also attenuated the loss of synaptic structure proteins, such as PSD-95, Munc18-1, and SNAP25. Treatment with EGb 761 for 5months inhibited microglial inflammatory activation in the brain. The effects of treatment with EGb 761 for 2months were weak and not statistically significant. Moreover, EGb 761 activated autophagy in microglia. Treatment with EGb 761 decreased Aß-induced microglial secretion of TNF-α and IL-1ß and activation of caspase-1, both of which were abolished by the inhibition of autophagy. Treatment with EGb 761 also reduced the concentrations of NLRP3 protein that colocalized with LC3-positive autophagosomes or autolysosomes in microglia. Additionally, long-term treatment with EGb 761 may reduce cerebral Aß pathology by inhibiting ß-secretase activity and Aß aggregation. Therefore, long-term treatment with G. biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology by antiinflammatory and Aß-directed mechanisms.

Mass spectroscopic characterisation of oligomeric proanthocyanidins derived from an extract of Pelargonium sidoides roots (EPs 7630) and pharmacological screening in CNS models.

Chromatographic fractionation of proanthocyanidin oligomers from an aqueous ethanolic extract of Pelargonium sidoides roots (EPs 7630) gave a diverse set of epigallo- and gallocatechin based oligomers, which are connected by A and B-type bonds. Additionally, two series of monosubstituted oligomers were detected by mass spectroscopy, sulphates and aminoconjugates. In vivo studies investigating motility, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities, showed no or only moderate pharmacological effects, indicating, that they have no intrinsic behavioural activities.

Quantification of allergenic urushiols in extracts of Ginkgo biloba leaves, in simple one-step extracts and refined manufactured material (EGb 761).

Extracts of leaves of Ginkgo biloba (family Ginkgoaceae), widely used in the treatment of peripheral and cerebral circulatory disorders as well as for dementia of different aetiology, contain long chain alkylphenols (with allergenic, cytotoxic, mutagenic and tumour-promoting properties) together with the extremely potent allergens, the urushiols. Such hazardous compounds can be present only in very low concentrations in phytopharmaceutical preparations and hence, for the purposes of drug safety, techniques must be available for the identification and quantification of these allergens at extremely low levels in refined manufactured materials. GC-MS analysis of samples collected at various stages during the production process of a standardised extract of G. biloba (EGb 761) demonstrated that all alkylphenols present in the primary acetone extracts were removed in parallel with the same efficiency irrespective of their aromatic substitution pattern. Furthermore, in the final product the content of urushiols was generally below the detection limit of 0.03 ppm. Therefore, it is concluded that demonstrating the absence of the predominant, and easily quantifiable, ginkgolic acids provides a reliable means for the control of pharmaceutical quality of the final product.

Rutin is essential for the antidepressant activity of Hypericum perforatum extracts in the forced swimming test.

It has been shown that aqueous alcoholic extracts of Hypericum perforatum (St. John's wort) are active in the forced swimming test (FST), an animal model for antidepressant activity. In this study, a series of ethanolic and methanolic extracts were investigated and, in almost all cases, the extracts showed strong activity. Only one methanolic research extract had no effect in the in vivo pharmacological experiments. Analytical characterisation using HPLC showed that the inactive extract had a reduced level of the diglycoside flavonoid rutin. Addition of rutin to the inactive extract, to produce a concentration within the normal range, resulted in a strong pharmacological effect comparable to that of the other extracts. First experiments suggest that this re-activation is not dose-dependent, indicating that rutin must be present above a threshold limit. It therefore appears vital that extracts of St. John's wort which are designed for the therapy of depressive disorders should be manufactured using plant material with sufficient amounts of rutin.