Toxicological evaluation of fucoidan from Undaria pinnatifidain vitro and in vivo.

The potential toxicity of fucoidan from Undaria pinnatifida was investigated in vitro and in vivo. By the Ames test, fucoidan showed no mutagenicity up to 500 microL/plate, and inhibited the mutagenicity induced by 4-nitro-quinoline-1-oxide, by up to 71%, compared with controls. In the bone marrow micronucleus test, fucoidan, at all levels tested, did not change the micronucleated polychromatic erythrocyte percentage ratio in mouse bone marrow cells. As an acute in vivo toxicity test, fucoidan from 0 to 2000 mg/kg body weight per day was administered orally to Sprague-Dawley rats for 28 days. No significant toxicological change was induced by fucoidan treatment up to 1000 mg/kg body weight per day in biochemical analyses, hematological analyses, necropsy and liver histopathology. The plasma ALT level was slightly, but significantly, increased in male rats at 2000 mg/kg/day. The consumption of fucoidan from Undaria pinnatifida, up to 1000 mg/kg body weight per day, may be safe in rodents, with no sign of toxicity after up to 28 days of daily administration.

Nanoemulsified green tea extract shows improved hypocholesterolemic effects in C57BL/6 mice.

Nanoemulsification of nutrients could improve bioavailability by enhancing intestinal uptake. We investigated the antioxidant and hypolipidemic effects of nanoemulsified green tea extract (NGTE). Antioxidant effect was measured by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assay and dichlorofluorescein diacetate (DCFH-DA) assay. C57BL/6 mice were fed a control high-fat diet, green tea extract (GTE), or NGTE diet for 4 weeks. In composition analysis, GTE and NGTE contained similar total catechin concentrations. The antioxidative effect of GTE was comparable with that of NGTE. In the ABTS assay, GTE had a marked effect, although NGTE was more effective than GTE in the DCFH-DA assay. In the mouse feeding experiment, total and low-density lipoprotein (LDL) cholesterol concentrations were significantly reduced after NGTE treatment in comparison with GTE treatment in high-fat-fed C57BL/6J mice over the course of 4 weeks. The hypocholesterolemic effects were greater in the NGTE group compared with the GTE group (24% vs. 15.4% LDL cholesterol reduction compared with the control). Expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly down-regulated. Protein expression of LDL receptor was significantly increased in the livers of both the GTE- and NGTE-treated groups (+234.1%, P<.01 and +274.7%, P<.001), with a greater effect in the NGTE than in the GTE group. Cholesterol 7α-hydroxylase gene expression was similarly increased in both the GTE and NGTE groups. These results suggest that nanoemulsification significantly increased hypocholesterolemic effects of GTE in vivo due to increased bioavailability.

Barley intake induces bile acid excretion by reduced expression of intestinal ASBT and NPC1L1 in C57BL/6J mice.

To investigate the hypocholesterolemic mechanism of barley in vivo, six-week-old C57BL/6J mice were fed a high-fat diet (HFD) or high-fat diet containing barley (HFD-B) for seven weeks. Total and LDL cholesterol concentrations were significantly reduced in the HFD-B group while fecal cholesterol and bile acid was increased. Real-time PCR and immunoblot analysis revealed the induction of FXR expression, which in turn suppressed the expression of ASBT and NPC1L1 in the HFD-B group compared with the controls. In the liver, the expression of HMG-CoA reductase was significantly reduced while LDL receptor expression was unaltered in the HFD-B group compared with the controls. Our data suggest that the hypocholesterolemic effects of barley are primarily the result of reduced dietary cholesterol uptake and bile acid resorption. Reduced expression of intestinal ASBT and NPC1L1 may play a key role in the regulation of dietary cholesterol and bile acid metabolism in mice consuming a diet containing barley.