Effects Of Pomegranate Ellagic Acid On Cholesterol And Lipid Metabolism In Golden Hamsters And Its Molecular Mechanism

This study was investigated the effects of Pomegranates Ellagic Acid (PEA) on blood cholesterol through the LXR/RXR/PPAR-ABCA1 nuclear receptors-signaling pathways, and on lipid metabolism through relevant gene expressions SREBP-lc, FAS and LPL on molecular level in hamsters. We reveal the molecular mechanism of PEA regulating the metabolism of cholesterol and lipid in hamsters. The research might provide certain reference for ellagic acid as dietary polyphenol to decrease morbidities of obesity, hyperlipidemia, atherosclerosis and metabolic syndrome.In the experiment, HPLC system determined polyphenol content of PEA. Hamsters were randomly divided into two groups, one (NG, n=9) was always fed the normal diet, and the high fat group (HFG, n=45) was fed a high fat diet at the first 4 weeks and then turned into the normal diet for the last 4 weeks. In HFG which was divided into five groups(n=9) during the last 4 weeks, three groups were treated with PEA by 44mg/kg.bw,88 mg/kg.bw and 177 mg/kg.bw, one group was treated with simvastatin by 1.77 mg/kg.bw, and one was given sterile double-distilled water. The amount of food consumed, body weight and food utility index were measured each week. At the end of week 4 and 8, plasma total cholesterol (TC), total triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and the total fecal bile acid were detected by using the kits. RT-PCR was used to analyze the expressions of hepatic LXRa, RXRa, PPARa, PPARy, ABCA1 and SREBP-lc, FAS, LPL on mRNA levels. The results we had found are as follows:1. In the current study, the high fat diet was able to increase body weight and food utility index without effect on food intake in the first four weeks. And significantly high levels of plasma TG and TC were induced by the high fat diet which illustrated that the hyperlipidemia model had been established.2. The data testified that PEA dose-dependently decreased plasma TG, TC, LDL-C, Non-HDL-C, HDL-C/TC and Non-HDL-C/HDL-C ratio, and promoted plasma HDL-C concentration. Dose-dependence existed and high dose PEA had the best effect.3. Dietary PEA promoted the removal of cholesterol through raising the excretion of bile acids. And high dose PEA was more effective than simvastatin.4. The result of RT-PCR revealed that PEA up-regulated liver X receptor (LXRa), peroxisome proliferator-activated receptor a (PPARa), peroxisome proliferator-activated receptor y (PPARy) and their downstream gene ATP-binding cassette transporter Al (ABCA1) with no effect on retinoid X receptor (RXRa). And high dose PEA was stronger than simvastatin in some respects. PEA promoted cholesterol removal through up-regulation of the two pathways LXR/PPAR-ABCA1.5. It was verified that PEA reduced plasma TC accompanied by down-regulation SREBP-1c、FAS mRNA and up-regulation LPL mRNA. PEA had dose-dependent and the similar effect with simvastatin even better than medicine in some respect.