Dehydroeffusol Pprevents Amyloid ß1-42-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn2+ Toxicity.

Dehydroeffusol, a phenanthrene isolated from Juncus effusus, is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer's disease, here we examined the effect of dehydroeffusol on amyloid ß1-42 (Aß1-42)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aß1-42 was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aß1-42 injection, was rescued by dehydroeffusol administration. Aß staining (uptake) was not reduced in the dentate granule cell layer by pre-administration of dehydroeffusol for 6 days, while increase in intracellular Zn2+ induced with Aß1-42 was reduced, suggesting that pre-administration of dehydroeffusol prior to Aß1-42 injection is effective for Aß1-42-mediated neurodegeneration that was linked with intracellular Zn2+ toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aß1-42-mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn2+-binding proteins, in the dentate granule cell layer, which can capture Zn2+ from Zn-Aß1-42 complexes. The present study indicates that pre-administration of dehydroeffusol protects Aß1-42-mediated neurodegeneration in the hippocampus by reducing intracellular Zn2+ toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aß1-42-induced pathogenesis in Alzheimer's disease.

Effect of polyphenol-rich extract from walnut on diet-induced hypertriglyceridemia in mice via enhancement of fatty acid oxidation in the liver.

The kernel pellicles of walnut are rich in ellagitannins with antioxidative activity. A polyphenol-rich extract from walnuts (WP, 45% polyphenol) was prepared and evaluated for its hypolipidemic effect in high fat diet fed mice. Oral administration of WP (100 and 200 mg/kg) significantly reduced liver weight and liver and serum triglycerides (TG). Hepatic beta-oxidation in cytosol, including peroxisome, was enhanced by WP (50-200 mg/kg). mRNA expressions of hepatic peroxisome proliferator-activated receptor (PPAR) alpha and acyl coenzyme A oxidase (ACOX) 1 were enhanced by WP (50-200 mg/kg). With respect to the hypotriglyceridemic mechanism of WP, it suppressed neither olive oil induced serum TG elevation in mice nor oleic acid induced TG accumulation in HepG2 cells. On the other hand, mRNA expressions of PPARalpha, ACOX1, and carnitine palmitoyltransferase (CPT) 1A in HepG2 cells were significantly enhanced by addition of WP (100 microg/mL). Moreover, tellimagrandin I, a polyphenolic constituent in WP, enhanced ACOX1 expression at 1-100 microg/mL. In conclusion, WP was found to possess hypotriglyceridemic activity via enhancement of peroxisomal fatty acid beta-oxidation in the liver. These results suggest that tellimagrandin I is involved in the hypotriglyceridemic mechanism of WP.

Effect of the walnut polyphenol fraction on oxidative stress in type 2 diabetes mice.

We examined the in vivo antioxidative effect of a polyphenol-rich walnut extract on oxidative stress in mice with type 2 diabetes. C57BL/KsJ-db/db mice were used as an accelerated oxidative animal model. The oral administration of the walnut polyphenol fraction at 200 mg/kg body weight for 4 weeks caused a significant decrease in the level of urinary 8-hydroxy-2'-deoxyguanosin, which is an in vivo marker of oxidative stress. These results imply that walnut polyphenols have both in vitro and in vivo antioxidant effects.

Anti-tumor promoting effect of glycosides from Prunus persica seeds.

Four minor components, along with the major cyanogenic glycosides, amygdalin and prunasin, were isolated from Prunus persica seeds (Persicae Semen; Tounin), and characterized as mandelic acid glycosides (beta-gentiobioside and beta-D-glucoside) and benzyl alcohol glycosides (beta-gentiobioside and beta-D-glucoside). The anti-tumor promoting activity of these compounds was examined in both in vitro and in vivo assays. All of the compounds significantly inhibited the Epstein-Barr virus early antigen activation induced by tumor promoter. In addition, they produced a delay of two-stage carcinogenesis on mouse skin that was comparable in potency to (-)-epigallocatechin gallate from green tea. Structure-activity relationships indicated that a substituent at the benzylic position with glycosidic linkage affected the in vitro and in vivo activities with an order of enhancing potency, CN