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Setosphapyrone C and D accelerate macrophages cholesterol effl ux by promoting LXRa/ABCA1 pathway
Ting Li,Jiayu Yin,Yubin Ji,Ping Lin,Yanjie Li,Zixun Yang,Shumei Hu,Jin Wang,Baihui Zhang,Saloni Koshti,Junfeng Wang,Chenfeng Ji,Shoudong Guo 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.8
LXRα agonists have attracted signifi cant attentiondue to their potential biological activities on promotingcholesterol effl ux. This study was designed to investigatewhether setosphapyrone C and D have potential lipid-loweringcapacity and the underlying mechanisms in vitro. Ourdata showed that setosphapyrone C and D had weak cytotoxicitycompared to the liver X receptor α (LXRα) agonistT0901317. In RAW 264.7 macrophages, setosphapyroneC and D signifi cantly enhanced [ 3 H]-cholesterol effl ux by~ 21.3% and 32.4%, respectively; furthermore, setosphapyroneC and D enhanced the protein levels of ATP-bindingcassette transporter (ABC) A1 and LXRα by 58% and 69%,and 60% and 70% (8 μM), respectively; however, they had noeff ect on the protein levels of ABCG1 and scavenger receptorB type 1; additionally, they had minor eff ect on the mRNAexpression of lipogenic genes. Of note, setosphapyrone C and D signifi cantly enhanced LXRα/ABCA1pathway inmice primary macrophages. In BRL cells, setosphapyroneC and D signifi cantly improved the protein levels of ABCA1and ABCG1; setosphapyrone D signifi cantly enhanced theprotein expression of low-density lipoprotein. Collectively,setosphapyrone C and D with weak cytotoxicity exhibitedeff ective lipid-lowering eff ect via enhancing LXRα/ABCpathways. Setosphapyrones possess potential applicationfor the treatment of hyperlipidemic diseases.