Setosphapyrone C and D accelerate macrophages cholesterol efflux by promoting LXRα/ABCA1 pathway - PubMed (original) (raw)

Comparative Study

. 2020 Aug;43(8):788-797.

doi: 10.1007/s12272-020-01255-w. Epub 2020 Aug 10.

Jiayu Yin 1 2, Yubin Ji 1, Ping Lin 2, Yanjie Li 2, Zixun Yang 1 2, Shumei Hu 2, Jin Wang 2, Baihui Zhang 1 2, Saloni Koshti 3, Junfeng Wang 4, Chenfeng Ji 5, Shoudong Guo 6 7

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Comparative Study

Setosphapyrone C and D accelerate macrophages cholesterol efflux by promoting LXRα/ABCA1 pathway

Ting Li et al. Arch Pharm Res. 2020 Aug.

Abstract

LXRα agonists have attracted significant attention due to their potential biological activities on promoting cholesterol efflux. This study was designed to investigate whether setosphapyrone C and D have potential lipid-lowering capacity and the underlying mechanisms in vitro. Our data showed that setosphapyrone C and D had weak cytotoxicity compared to the liver X receptor α (LXRα) agonist T0901317. In RAW 264.7 macrophages, setosphapyrone C and D significantly enhanced [3H]-cholesterol efflux by ~ 21.3% and 32.4%, respectively; furthermore, setosphapyrone C and D enhanced the protein levels of ATP-binding cassette transporter (ABC) A1 and LXRα by 58% and 69%, and 60% and 70% (8 µM), respectively; however, they had no effect on the protein levels of ABCG1 and scavenger receptor B type 1; additionally, they had minor effect on the mRNA expression of lipogenic genes. Of note, setosphapyrone C and D significantly enhanced LXRα/ABCA1pathway in mice primary macrophages. In BRL cells, setosphapyrone C and D significantly improved the protein levels of ABCA1 and ABCG1; setosphapyrone D significantly enhanced the protein expression of low-density lipoprotein. Collectively, setosphapyrone C and D with weak cytotoxicity exhibited effective lipid-lowering effect via enhancing LXRα/ABC pathways. Setosphapyrones possess potential application for the treatment of hyperlipidemic diseases.

Keywords: ATP-binding cassette transporter; Hyperlipidemia; LXR antagonist; Reverse cholesterol transport.

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