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Ishihara Y.,Hiroshima University | Ishihara Y.,Tokushima Bunri University | Itoh K.,Tokushima Bunri University | Mitsuda Y.,Tokushima Bunri University | And 10 more authors.
Free Radical Research | Year: 2013

Oxidative stress is considered to be related to the onset and/or progression of Alzheimer's disease (AD), but there is insufficient evidence of its role(s). In this study, we evaluated the relationships between the brain redox state and cognitive function using a triple transgenic mouse model of AD (3 × Tg-AD mouse). One group of 3 × Tg-AD mice started to receive an α-tocopherol-supplemented diet at 2 months of age and another group of 3 × Tg-AD mice was fed a normal diet. The levels of α-tocopherol, reduced glutathione, oxidized glutathione, and lipid peroxidation were decreased in the cerebral cortex and hippocampus at 4 months of age in the 3 × Tg-AD mice fed a normal diet. These reductions were abrogated by the supplementation of α-tocopherol in the diet. During Morris water maze testing, the 3 × Tg-AD mice did not exhibit cognitive impairment at 4 months of age, but started to show cognitive dysfunction at 6 months of age, and α-tocopherol supplementation suppressed this dysfunction. Magnetic resonance imaging (MRI) using 3-hydroxymethyl-proxyl as a probe showed decreases in the signal intensity in the brains of 3 × Tg-AD mice at 4 months of age, and this reduction was clearly attenuated by α-tocopherol supplementation. Taken together, these findings suggest that oxidative stress can be associated with the cognitive impairment in 3 × Tg-AD mice. Furthermore, MRI might be a powerful tool to noninvasively evaluate the increases in reactive radicals, especially those occurring during the early stages of AD. © 2013 Informa UK, Ltd.

Kuhn C.,TU Dresden | Arapogianni N.E.,Laboratory of Pharmacognosy and Natural Products Chemistry | Halabalaki M.,Laboratory of Pharmacognosy and Natural Products Chemistry | Hempel J.,TU Dresden | And 4 more authors.
Planta Medica | Year: 2011

A number of medicinal/culinary herbs have been reported to improve glucose metabolism and to yield hypoglycemic effects in patients with diabetes. Since stimulation of insulin sensitivity appears to be a potential mechanism, peroxisome proliferator-activated receptor (PPAR) is a likely target molecule for small lipophilic compounds derived from endogenous metabolism and nutrition. Functionally, PPAR integrates the control of energy, lipid, and glucose homeostasis. In addition, PPAR activity is involved in energy expenditure. Therefore the aim of this study was to investigate whether PPAR and PPAR as well as the stimulation of glucose uptake is activated by botanical products. Cistus salvifolius (Cistaceae) has been identified as a candidate botanical in a preliminary screening of extracts from medicinal plants of Greek flora. In a bioguided approach, crude extracts, fractions and in the end purified compounds have been evaluated for PPAR and PPAR specific activities using cell-based transactivation assays. Glucose uptake was measured by nonradioactive 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) uptake. Concerning PPAR several extracts induced reporter gene activity, and clear dose-response patterns (0.1-100 g/mL) could be established in the case of the cyclohexane and dichloromethane extracts. Isolation of individual compounds from the cyclohexane extract revealed that at least 6 out of 7 compounds isolated were active with trans-cinnamic acid showing a clear dose-response pattern. In contrast, they were found to be inactive on PPAR. The same compounds, however, were also active in stimulating glucose uptake into 3T3-L1 adipocytes. In summary, the bioguided fractionation of Cistus salvifolius yields PPAR stimulating metabolites with differing chemical natures. In conclusion, PPAR represents a candidate molecule for the mediation of improvement of glucose metabolism by botanical/nutritional products. © Georg Thieme Verlag KG Stuttgart New York.

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