Protective effects of caffeic acid (CA) and ellagic acid (EA) in kidney of diabetic mice were examined. CA or EA at 2.5 and 5% was mixed in diet and supplied to diabetic mice for 12 wk. Results showed that the intake of CA or EA increased renal content of these compounds, alleviated body weight loss, decreased urine output, increased plasma insulin and decreased blood glucose levels at weeks 6 and 12 (p<0.05). The intake of these compounds dose dependently reduced plasma blood urea nitrogen and elevated creatinine clearance (p<0.05). CA or EA at 5% significantly decreased the levels of plasma HbA1c, urinary glycated albumin, renal carboxymethyllysine, pentosidine, sorbitol and fructose (p<0.05), and significantly diminished renal activity of aldose reductase and sorbitol dehydrogenase, as well as suppressed renal aldose reductase mRNA expression (p<0.05). CA or EA dose dependently lowered renal levels of IL-6, IL-1beta, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein 1 (MCP-1) (p<0.05). Furthermore, CA or EA dose dependently down-regulated tumor necrosis factor-alpha and monocyte chemoattractant protein-1 mRNA expression in kidney (p<0.05). Based on the observed anti-glycative and anti-inflammatory effects, the supplement of CA or EA might be helpful for the prevention or attenuation of diabetic kidney diseases.

The antibacterial effects of roselle calyx aqueous and ethanol extracts and protocatechuic acid against food spoilage bacteria Salmonella typhimurium DT104, Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, and Bacillus cereus were examined. Minimal inhibitory concentrations of roselle calyx aqueous and ethanol extracts and protocatechuic acid against these bacteria were in the range of 112-144, 72-96, and 24-44 microg/mL, respectively. Protocatechuic acid content in roselle calyx aqueous and ethanol extracts was 2.8 +/- 0.7 and 11.9 +/- 1.2 mg/g, respectively. Antibacterial activity of roselle calyx ethanol extract and protocatechuic acid was not affected by heat treatments from 25 degrees to 75 degrees C and 25 degrees to 100 degrees C, respectively. After 3 days storage at 25 degrees C, the addition of roselle calyx extracts and protocatechuic acid exhibited dose-dependent inhibitory effects against test bacteria in ground beef and apple juice, in which the roselle calyx ethanol extract showed greater antibacterial effects than the aqueous extract. These data suggest that roselle calyx ethanol extract and protocatechuic acid might be potent agents as food additives to prevent contamination from these bacteria.

The 8ab protein of SARS-CoV is a group-specific accessory protein, which is lost when the virus was transmitted from animals to humans due to a 29-nucleotide deletion in the ORF8ab region. Here we found that 8ab protein is associated with ER membrane at luminal surface. 8ab protein was found to up-regulate the synthesis of endogenous ER-resident chaperons involved in protein folding through the activation of the transcription factor ATF6, while it showed no effect on the CHOP induction and XBP1 splicing associated with the unfolded protein response (UPR). When ectopically expressed in mammalian cells, 8ab induced the proteolysis of ATF6 and the translocation of its cleaved DNA-binding and transcription-activation domains from the ER to the nucleus. Finally, we showed that 8ab binds to the luminal domain of ATF6. These findings suggest that 8ab could modulate the UPR by activating ATF6 to facilitate protein folding and processing. Thus, the loss of 8ab in SARS-CoV through viral evolution in animals may play a role in its pathogenicity.

Oxidized LDL (oxLDL) and its component hydroxy fatty acids were shown to activate peroxisome proliferator-activating receptor alpha (PPARalpha) and gamma (PPARgamma). To test the hypothesis that lipid oxidation products in oxidized frying oil (OFO) can activate PPARalpha and up-regulate its target genes, a feeding experiment and a transactivation experiment were conducted. Based on a 2 x 2 factorial design, four groups of Sprague-Dawley male weanling rats were fed diets containing either high (20 g/100 g, HO and HF) or low (5 g/100 g, LO and LF) levels of oxidized frying soybean oil (HO and LO) or fresh soybean oil (HF and LF) for 6 wk. The OFO sample was prepared by frying wheat dough sheets in soybean oil at 205 +/- 5 degrees C for 24 h. OFO dose dependently and significantly increased (P < 0.05) mRNA of acyl-CoA oxidase (ACO) and cytochrome P(450) 4A1(CYP4A1) in liver of rats. Dietary OFO also dose dependently increased liver microsomal CYP4A protein (P < 0.05). The activity of hepatic ACO of the HO group was sixfold that of the HF group (P < 0.05). Plasma total lipids, liver triglycerides, cholesterol and total lipids were reduced in rats fed the LO and HO diets (P < 0.05). Through the ligand binding domain of PPARalpha, the hydrolyzed OFO enhanced the expression of alkaline phosphatase (ALP) reporter gene to a significantly greater extent (P < 0.05) than the hydrolyzed fresh soybean oil in a transactivation assay using a clone of CHO K1 cells stably expressing Gal4-PPARalpha chimeric receptor and UAS4-ALP reporter. The results support our hypothesis that dietary OFO, by activating PPARalpha, up-regulates the expression of PPARalpha downstream genes and alters lipid metabolism in rats.

No abstract