Effects of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in L-02 human hepatic cells via the PPARγ-ABCA1/CYP7A1 pathway

• Published in: Food & function 2016-12, Vol.7 (12), p.4976-4983
• Main Authors: Lv, Ou, Wang, Lifang, Li, Jianke, Ma, Qianqian, Zhao, Wei
• Format: Article
• Language: English
• Subjects: ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; Cell Line; Cholesterol - metabolism; Cholesterol 7-alpha-Hydroxylase - genetics; Cholesterol 7-alpha-Hydroxylase - metabolism; Gene Expression Regulation - drug effects; Hepatocytes - drug effects; Lipid Metabolism - drug effects; Molecular Structure; Polyphenols - chemistry; Polyphenols - pharmacology; PPAR gamma - drug effects; PPAR gamma - metabolism; Punicaceae - chemistry
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c6fo01261b

To study the effect of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in human hepatic cells, purified pomegranate peel polyphenols (PPPs), their main component, punicalagin (PC), and the metabolite of PC, pomegranate ellagic acid (PEA), were chosen as the polyphenols to be tested. At the same time the human hepatocyte cell line L-02 was selected as the experimental cell and a model of steatotic L-02 hepatocytes in vitro was constructed in this paper. The results showed that PPPs, PC and PEA in different concentrations could decrease the total cholesterol (TC) content and increase the total bile acid (TBA) content, and so possess a lipid-lowering effect. The order of the lipid-lowering effect from strong to weak is PEA > PPPs > PC. The relative mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), ATP-binding cassette transporter A1 (ABCA1) and cholesterol 7α hydroxylase (CYP7A1) was up-regulated by PPPs, PC and PEA in a dose-dependent manner. The effect on the relative mRNA expression can be listed in descending order as: PEA > PPPs > PC. Similar results were found in a western blot analysis. The PPARγ protein, ABCA1 protein and CYP7A1 protein were up-regulated in L-02 cells treated with the three tested polyphenols. All the results indicated that PPPs, PC and PEA could regulate upstream the expression of PPARγ, ABCA1 and CYP7A1, both at transcript and protein levels, to activate the PPARγ-ABCA1/CYP7A1 cell signaling pathway and enhance cholesterol metabolism in L-02 cells. Therefore, PPPs, as a kind of natural material, may be paid more attention in the prevention and treatment of diseases related to excessive cholesterol accumulation. PPPs, PC and PEA in different concentrations were found to decrease the total cholesterol (TC) content and increase the total bile acid (TBA) content of a human hepatic cell model, and so possess a lipid-lowering effect.