Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis

Abstract

Objective: To seek out the effect of curcumin on cholesterol efflux in THP-1 macrophages and clarify its specific mechanism. Methods: THP-1 macrophages were cultured with curcumin at different concentrations, followed by detection of the toxicity of curcumin to cells utilizing CCK-8 assay. Following culturing with serum-free ox-LDL, THP-1 macrophages were transfected with mi-miR-125a-Sp, or in-miR-125a-5p, or pcDNA3.1-SIRT6, or si-SIRT6 for 24 hr, prior to treatment with curcumin  at different concentrations. Oil red O staining was applied to examine the formation rate of foam cells, the kits were used for measuring intracellular lipid content of THP-1 macrophages, and the fluorescence detection kit for observing the cholesterol efflux rate. The expressions of miR-125a-Sp, SIRT6, and ABCA were assayed by qRT-PCR and Western blot. ELISA was adopted to assess the contents of TNF-a, IL-6, and MCP-1. The interaction between miR-125a-5p and SIRT6 was evaluated by dual-luciferase reporter gene assay. Results: The optimal dosage of curcumin could reduce foam cell formation and intracellular lipid content, and promote cholesterol efflux in THP-1 macrophages. Meanwhile, curcumin markedly suppressed the expression of miR-125a-5p and upregulated the expression of SIRT6. MiR-125a-Sp negatively targeted SIRT6. Overexpression of SIRT6 partially reversed the inhibition role of miR-125a-5p mimic in the biological function of curcumin. Silencing of SIRT6 could partially reverse the effect of the miR-125a-5p inhibitor on the biological function of curcumin. Conclusion: Curcumin could promote cholesterol efflux of THP-1 macrophages through miR-125a-Sp/SIRT6 axis and regulate the expression of ABCA1.