Erythrodiol, an Olive Oil Constituent, Increases the Half-Life of ABCA1 and Enhances Cholesterol Efflux from THP-1-Derived Macrophages

Abstract

Cholesterol efflux (ChE) from macrophages is an initial step of reverse cholesterol transport (RCT). The ATP-binding cassette transporter A1 (ABCA1) is a key transporter for ChE and its increased expression is regarded to attenuate atherosclerosis. Thus, the identification and characterization of molecules raising ABCA1 and thereby stimulating ChE is of pharmacological relevance. In this study, we tested dietary compounds from olive oil for their capacity of enhancing cellular ABCA1 protein level. We identified erythrodiol (Olean-12-ene-3β,28-diol) as an ABCA1 stabilizer and revealed its positive influence on ChE in THP-1-derived human macrophages. Among the nine tested compounds from olive oil, erythrodiol was the sole compound raising ABCA1 protein level (at 10 μM). None of the tested compounds impaired viability of THP-1 macrophages from 5 to 20 μM as determined by resazurin conversion. Western blot analyses of key membrane transporters contributing to ChE showed that the protein level of ABCG1 and scavenger receptor class B member 1 (SR-B1) remain unaffected by erythrodiol. Besides, erythrodiol (10 μM) did not influence the mRNA level of ABCA1, ABCG1, and SR-B1, as determined by quantitative reverse transcription PCR, but significantly inhibited the degradation of ABCA1 as evident by an increased half-life of the protein in the presence of cycloheximide, an inhibitor of de novo protein synthesis. Therefore, erythrodiol promotes ChE from THP-1-derived human macrophages by stabilizing the ABCA1 protein. This bioactivity makes erythrodiol a good candidate to be further explored for therapeutic or preventive application in the context of atherosclerosis.

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

“…Recently, a study was conducted in THP-1 macrophages to screen the effect of various components of olive oil on foam cell formation. The results showed that among several compounds, only erythrodiol (10 mM) has a positive effect on ApoA-1mediated cholesterol efflux by inhibiting ABCA1 degradation (Wang et al, 2017f). Therefore, erythrodiol may serve as a good candidate for further studies related to the prevention of atherosclerosis progression.…”

“…Increased ApoA-1mediated cholesterol efflux by inhibiting ABCA1 degradation in THP-1 macrophages (Wang et al, 2017f).…”

Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

“…It have been also described that hesperetin, a citrus flavonoid, increased ABCA1 promoter and LXR enhancer activities in THP-1 macrophages [ 139 ]. Recently, dietary compounds from olive oil were tested for their capacity to enhance cellular ABCA1 protein level, and authors identified erythrodiol (Olean-12-ene-3b,28-diol) as an ABCA1 stabilizer [ 140 ]. Additionally, the mRNA and protein expression of LXRs and their target genes, including ABCA1 , was significantly increased in macrophages stimulated with cineole [ 141 ].…”

The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot †

“…Emodin, an anthraquinone derivative isolated from the roots of Rheum palmatum , enhanced cholesterol efflux by activating PPARγ in ox-LDL-loaded THP1 macrophages [ 135 ]. Erythrodiol from olive oil promoted cholesterol efflux from THP-1-derived macrophages by stabilizing the ABCA1 protein [ 136 ]. Leoligin, a natural lignan found in Edelweiss ( Leontopodium nivale ssp.…”