Zerumbone, A Natural Cyclic Sesquiterpene, Promotes ABCA1-Dependent Cholesterol Efflux from Human THP-1 Macrophages

This study was conducted to explore the effect of zerumbone, isolated from Zingiberzerumbet Smith, on apolipoprotein A-I (apoA-I)-mediated cholesterol efflux from THP-1 macrophages. THP-1 macrophages were treated with different concentrations (10-100 μmol/l) of zerumbone and cholesterol efflux was measured. The involvement of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 and ERK1/2 signaling was checked. Notably, zerumbone caused a concentration-dependent induction of ABCA1 but not ABCG1, coupled with enhanced phosphorylation of ERK1/2. Pre-treatment with PD98059 (a potent ERK1/2 inhibitor) significantly blocked the upregulation of ABCA1 by zerumbone. Small interfering RNA-mediated downregulation of ABCA1 but not ABCG1 significantly impaired the promotion of apoA-I-mediated cholesterol efflux by zerumbone. Taken together, zerumbone has the capacity to facilitate apoA-I-mediated cholesterol efflux from macrophages through the activation of ERK1/2 signaling and upregulation of ABCA1.