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There are two isoforms of apolipoprotein B (apoB) in mammals: apoB-100 and apoB-48. The latter is generated by C-to-U editing of apoB mRNA, catalyzed by the apolipoprotein B mRNA editing enzyme, namely, catalytic polypeptide 1 (APOBEC-1). Lipid particles containing apoB-48 are cleared from the plasma more rapidly than those containing apoB-100 and thus do not contribute to plaque formation in the arterial wall. In the present study, we analyzed whether curcumin is capable of regulating lipid metabolism by improving the level of apoB mRNA editing. The cytotoxicity of curcumin in hepatocytes was determined using the 3-(4,5-dimethylthiazol‑2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the levels of APOBEC-1 mRNA and protein were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting. The efficiency of apoB mRNA editing was determined by reverse transcription PCR (RT-PCR) products and cloning sequencing analysis. We demonstrated that curcumin concentrations up to 70 µM had no significant cytotoxic effects on primary rat hepatocytes at 24 h. At 15 µM, curcumin significantly increased the expression of APOBEC-1 mRNA and protein, and increased the editing level of apoB mRNA from 3.13 to 7.53%. At 25 µM, curcumin reduced the expression of APOBEC-1; however, it did not affect the apoB mRNA editing level. Our data suggested that curcumin at a concentration of 15 µM raised the level of apoB-48 and reduced the level of apoB-100 by increasing the expression of APOBEC-1 in primary rat hepatocytes; therefore, curcumin may be a novel preventative therapy for atherosclerosis.

To investigate the molecular mechanisms of the effect of curcumin on up-regulation of LDL receptor expression, a sterol regulatory report system was established in Xenopus laevis oocytes by microinjection of a plasmid pLXRN-4SRE-fPA, in which green fluorescence protein (GFP) gene was constructed downstream from the sterol regulatory element-1 (SRE-1), in the nucleus of the oocytes. The oocytes were treated with different kinds of natural medicines: curcumin, tea polyphenols, tanshinone, ligustrazine, ginkgolide, astragalosides. The expression of GFP was induced only by curcumin. In addition, it was also proved that the curcumin can increase the expression of functional LDL receptors in human liver hepatoma cell line HepG2. In conclusion, curcumin may up-regulate the expression of LDL receptor by its effect on SRE pathway.