Processing of the platelet amyloid precursor protein in the mild cognitive impairment (MCI).

It has been suggested that mild cognitive impairment (MCI) patients deteriorate faster than the healthy elderly population and have an increased risk of developing dementia. Certain blood molecular biomarkers have been identified as prognostic markers in Alzheimer's disease (AD). The present study was aimed to assess the status of the platelet amyloid precursor protein (APP) metabolism in MCI and AD subjects and establish to what extent any variation could have a prognostic value suggestive of predictive AD in MCI patients. Thirty-four subjects diagnosed with MCI and 45 subjects with AD were compared to 28 healthy elderly individuals for assessing for protein levels of APP, ß-APP cleaving enzyme 1 (BACE1), presenilin 1 (PS1) and a disintegrin and metalloproteinase-10 (ADAM-10) by western blot, and for the enzyme activities of BACE1 and γ-secretase by using specific fluorogenic substrates, in samples of platelets. A similar pattern in the healthy elderly and MCI patients was found for BACE1 and PS1 levels. A reduction of APP levels in MCI and AD patients compared with healthy elderly individuals was found. Augmented levels of ADAM-10 in both MCI and AD were displayed in comparison with age-matched control subjects. The ratio ADAM-10/BACE1 was higher for the MCI group versus AD group. Whereas BACE1 and PS1 levels were only increased in AD regarding to controls, BACE1 and γ-secretase activities augmented significantly in both MCI and AD groups. Finally, differences and similarities between MCI and AD patients were observed in several markers of platelet APP processing. Larger sample sets from diverse populations need to be analyzed to define a signature for the presence of MCI or AD pathology and to early detect AD at the MCI stage.

Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids isolated from Tanacetum microphyllum.

Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some flavonoids have been reported previously to inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The present study focuses on the effect of various naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) on modulation of lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in RAW 264.7 cells. Western blotting showed that all flavonoids suppressed the induction of both iNOS and COX-2. Ermanin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol were the most potent inhibitors. This study suggests that inhibition of iNOS and COX-2 expression by flavonoids may be one of the mechanisms responsible for their anti-inflammatory effects, and that they may be potential agents for use in the treatment of inflammatory diseases.

Flavonoids and a sesquiterpene lactone from Tanacetum microphyllum inhibit anti-inflammatory mediators in LPS-stimulated mouse peritoneal macrophages.

In our ongoing research into anti-inflammatory compounds from Tanacetum microphyllum, four naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) and one sesquiterpene lactone (hydroxyachillin) isolated from this plant, were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These five compounds significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) in a concentration-dependent manner. In the tumour necrosis factor-alpha (TNF-alpha) assay, only centaureidin and hydroxyachillin significantly inhibited the accumulation of TNF-alpha. These results indicate that these compounds may contribute to the anti-inflammatory properties of T. microphyllum.