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KMID : 0043320200430080788
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Archives of Pharmacal Research
2020 Volume.43 No. 8 p.788 ~ p.797
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Setosphapyrone C and D accelerate macrophages cholesterol efflux by promoting LXRα/ABCA1 pathway
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Li Ting
Yin Jiayu
Ji Yubin
Lin Ping
Li Yanjie
Yang Zixun
Hu Shumei
Wang Jin
Zhang Baihui
Koshti Saloni
Wang Junfeng
Ji Chenfeng
Guo Shoudong
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Abstract
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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.
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KEYWORD
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LXR antagonist, Reverse cholesterol transport, Hyperlipidemia, ATP-binding cassette transporter
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