Abstract:

Objective To investigate the effects of berberine on cholesterol efflux in THP-1 macrophage derived foam cells, and explore the possible mechanism. Methods HP-1 cells were induced into macrophages by phorbol myristate acetate (PMA), and were treated with acetylated low-density lipoprotein (Ac-LDL) to establish the THP-1 macrophage derived foam cell models. Foam cells were divided into blank control group and berberine (5 to 20 μmol/L) treatment groups according to the way of treatment and berberine concentrations. After treatment for 24 h, flow cytometry was employed to detect Ac-LDL aggregation, enzymic method was adopted to detect contents of cholesterol and triglyceride, scintillation counting technique was used to detect cholesterol efflux, and effects of peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662 pretreatment on cholesterol efflux (pioglitazone as positive control) were analysed. Besides, RT-PCR was applied to detect expression of liver X receptor α (LXRα) and ATP binding cassette transporter A1 (ABCA1) mRNA. Results Compared with blank control group, Ac-LDL aggregation and contents of cholesterol and triglyceride of foam cells in various berberine treatment groups decreased significantly (P＜0.01), while cholesterol efflux increased (P＜0.01) in a dose-dependent manner. After GW9662 pretreatment, there was no significant difference in cholesterol efflux between various berberine treatment groups and control group (P>0.05). Furthermore, expression of LXRα and ABCA1 mRNA of foam cells in various berberine treatment groups was higher than that in blank control group. Conclusion Berberine may increase cholesterol efflux in THP-1 macrophage derived foam cells, the mechanism of which may be associated with activation of PPARγ pathway and increase of expression of LXRα and ABCA1 mRNA.

Key words: berberine, foam cell, cholesterol, ATP binding cassette transporter A1, peroxisome proliferator-activated receptor-γ, liver X receptor α