Effects of ellagic acid-rich extract of pomegranates peel on regulation of cholesterol metabolism and its molecular mechanism in hamsters.

The study investigated the effect of pomegranates ellagic acid (PEA) on blood cholesterol and investigated its effects on LXR/RXR/PPAR-ABCA1 nuclear receptors-signaling pathways of cholesterol metabolism on molecular level in hamsters. In this experiment, hamsters were randomly divided into two groups: the first group (NG, n = 9) was always fed the normal diet, whereas the other group (HFG, n = 45) was fed a high fat diet during the first 4 weeks and then fed 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 at 44 mg per kg bw, 88 mg per kg bw and 177 mg per kg bw, one group was treated with simvastatin at 1.77 mg per kg bw, and one was given sterile double-distilled water. The data validated that PEA dose-dependently decreased plasma total cholesterol and triglyceride level accompanied by a greater excretion of fecal bile acid. The result of RT-PCR revealed that PEA up-regulated liver X receptor (LXRα), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ) and their downstream gene ATP-binding cassette transporter A1 (ABCA1), with no effect on retinoid X receptor (RXRα). PEA promoted cholesterol removal by enhancing fecal bile acid and up-regulation of the two pathways, LXR/PPAR-ABCA1. Moreover, PEA was stronger than simvastatin in some aspects.

In vitro steatosis hepatic cell model to compare the lipid-lowering effects of pomegranate peel polyphenols with several other plant polyphenols as well as its related cholesterol efflux mechanisms.

This study was aimed to compare the relative activities of the purified pomegranate peels polyphenols (PPPs) with some other plant polyphenols including punicalagin, ellagic acid, gallic acid, phlorizin, and epigallocatechin gallate (EGCG) on the lipid metabolism regulation, and the cholesterol efflux mechanisms of PPPs and punicalagin were also investigated. In this paper, a convenient and accurate in vitro HL7702 steatosis hepatic cell model was applied to evaluate the lipid-lowering effects of the tested polyphenols. The results showed that PPPs possessed the strongest lipid-lowering effects. Prevention group (treated with polyphenols when establishing of steatosis model) was more effective than treatment group (treated with polyphenols after establishment of steatosis model). Punicalagin displayed the strongest lipid-lowering effects among all the tested components of pomegranate peel polyphenols. Moreover, PPPs and punicalagin (10, 20, 40 µg/mL) significantly increased the mRNA expression of LXRα (Liver X receptor alpha) and its target genes-ABCA1 (ATP-binding cassette transporter A1) in a dose-dependent manner in HL7702 steatosis hepatic cells. The high mRNA expression of LXRα and ABCA1, next to lovastatin, was observed in cells treated with 40 µg/mL of PPPs. These in vitro findings suggested that PPPs might have great potential in the clinic treatment of hyperlipemia.