No abstract

Paclitaxel is indispensable in treating human cancers. Due to poor drug solubility and efflux systems in the gastrointestinal tract, peroral delivery of paclitaxel has been a significant challenge. We developed a mucoadhesive oral formulation (DHP107) that can directly and effectively deliver paclitaxel to intestinal endothelial cells without concomitant use of P-glycoprotein inhibitors.

No abstract

No abstract

Three major sources of flavonoids and phenolic compounds, which are commonly used in food industry, namely loquat leaf (LL), grape skin (GS) and acai puree, were tested in regard to their potential anti-atherosclerotic and anti-diabetic activity. The compounds were evaluated by in vitro antioxidant assay using a macrophage model and for in vivo hypolipidemic activity using zebrafish. In assays in vitro, all extracts demonstrated potent ferric ion reductive capacity, radical-scavenging activity and inhibition of low-density lipoprotein (LDL) oxidation at a final concentration of 0.1 mg/ml. Extracts could also abrogate fructose-mediated protein glycation and mildly inhibit cholesteryl ester transfer protein (CETP). Cellular uptake of oxidized or acetylated LDL into macrophages was inhibited by acai treatment (final concentration, 0.1 mg/ml) and moderately diminished by GS and LL extracts. After 4 weeks of feeding on a high cholesterol diet (HCD), zebrafish exhibited serum total cholesterol (TC) and triglyceride (TG) levels 2.5-fold higher than those fed a normal diet (ND). Within the experimental group, those fed acai demonstrated the lowest serum TC and CETP activity, while the LL-consuming group showed a reduction in serum TC and TG relative to HCD-fed fish. Serum glucose levels also increased in the HCD group, to threefold above the ND group; GS and LL feeding elicited the greatest reduction in hyperglycemia. The groups consuming acai and LL showed much less hepatic inflammation, as well as attenuation of fatty liver and a reduced content of oxidized species. In conclusion, extracts of LL, GS, and acai shared antioxidant, anti-inflammatory and anti-atherosclerotic activity in cellular assays and in a hypercholesterolemic zebrafish model.

Culinary herbs and spices have been widely used for their hypoglycemic, lipid-lowering, and anti-inflammatory activities. This study examined the physiologic activity of hydrophilic components using extracts of turmeric or laurel leaf powder. Aqueous extracts of turmeric and laurel showed potent inhibitory activity against fructose-mediated glycation with antioxidant ability against low-density lipoprotein (LDL) oxidation and radical scavenging activity. The turmeric and laurel extracts had potent cholesteryl ester transfer protein (CETP) inhibitory ability (up to 23% and 40% inhibition, respectively) at a final concentration of 10 μg/mL. The turmeric and laurel extracts inhibited the cellular uptake of oxidized LDL into macrophages, which is the initial step in atherogenesis. For in vivo testing, zebrafish consumed a high cholesterol diet (HCD) (final concentration, 4% [wt/wt]) with or without turmeric or laurel powder (final concentration, 10% [wt/wt]). The turmeric and laurel groups had a 14% and 12% decrease, respectively, in the weight and height ratios compared to the HCD group. The plasma total cholesterol level was significantly lower in the turmeric and laurel groups (48% and 28% less, respectively, than in the HCD group). Plasma triglycerides were more markedly reduced in the turmeric and laurel groups than in the HCD group (68% and 56% less, respectively, than the HCD group). In conclusion, the hydrophilic extracts of turmeric and laurel potently suppressed the incidence of atherosclerosis via a strong antioxidant potential, prevention of apolipoprotein A-I glycation and LDL phagocytosis, and inhibition of CETP. Consumption of turmeric and laurel extracts exhibited hypolipidemic and antioxidant activities in a hypercholesterolemic zebrafish model.

It is feasible to use an iodized oil emulsion system for the intratumoral transfection of nonviral vectors in experimentally induced hypervascular hepatic tumors.

A functional oil containing diacylglycerol (DAG) and monoacylglycerol (MAG) has been shown to have a strong anti-atherosclerotic effect in a mouse model. Among the lipid components, MAG is responsible for the beneficial effect with an enhanced antioxidant effect in the mouse model. In this report, several MAG-containing fatty acids (MAG-oleic acid [MAG-O], MAG-palmitic acid [MAG-P], and MAG-stearic acid [MAG-S]) were synthesized, and the antioxidant and anti-atherogenic activities were evaluated in vitro and in a cellular model. MAG-O had the strongest radical scavenging and antioxidant activities against copper-mediated low-density lipoprotein (LDL) oxidation and the strongest inhibitory activity against LDL-associated phospholipase A(2) and exhibited potent activation of paraoxonase activity, which contributes to the maintenance of antioxidant activity. All MAG species in this study exhibited inhibitory activity against glycation of apolipoproteins, in contrast to DAG. Oxidized LDL uptake into THP-1 cells was strongly inhibited by MAG-O treatment at a final concentration of 20 microM. MAG-O-treated cell culture medium showed the lowest production of malondialdehyde and lipid hydroperoxide compared to MAG-S and MAG-P. In conclusion, MAG-O had potent antioxidant, antidiabetic, and anti-atherogenic effects in vitro and in a cellular model.