Berberine-induced inhibition of adipocyte enhancer-binding protein 1 attenuates oxidized low-density lipoprotein accumulation and foam cell formation in phorbol 12-myristate 13-acetate-induced macrophages

Abstract

The phagocytosis of oxidized low-density lipoprotein (oxLDL) by monocyte-derived macrophages and the subsequent differentiation of macrophages into foam cells are the key steps in atherogenesis. Scavenger receptors, such as CD36 and lectin-like low-density lipoprotein receptor 1 (LOX-1), are responsible for the uptake of oxLDL. Adipocyte enhancer-binding protein 1 (AEBP1) regulates many key genes associated with intracellular cholesterol efflux. The present study investigated the function of berberine, a compound isolated from Rhizoma coptidis, on foam cell formation, and explored the possible underlying mechanism. We found that berberine inhibited the oxLDL uptake of macrophages and reduced foam cell formation in a dose-dependent manner. Moreover, AEBP1 expression in macrophages increased and decreased after oxLDL and berberine treatments in a dose-dependent manner, respectively. Berberine reduced the expression of scavenger receptors CD36 and LOX-1, but did not affect the expression of CD68 in oxLDL-stimulated macrophages. Overall, berberine reduced foam cell formation by a dual mechanism, which decreased oxLDL internalization via the suppression of CD36 and LOX-1, and increased cholesterol efflux by inhibiting AEBP1 expression in macrophages.