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

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.

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Acknowledgements

This work was supported by Natural Science Foundation of China (81770463, 31300639), Shandong Provincial Natural Science Fund (ZR2013HQ014), Medicine & Health Scientific Technology Development Program of Shandong Province (2018WS064), and Study Abroad Fund of Weifang Medical University. We thank Guanghai Zhou at Shandong First Medical University & Shandong Academy of Medical Sciences for providing help in performing the isotope tracing assay.

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Author notes

1. Ting Li, Jiayu Yin and Yubin Ji have contributed equally to this work.

Authors and Affiliations

1. College of Pharmacy Engineering Research Center for Medicine, Harbin University of Commerce, 150076, Harbin, China
   Ting Li, Jiayu Yin, Yubin Ji, Zixun Yang, Baihui Zhang & Shoudong Guo
2. Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, 261053, Weifang, China
   Ting Li, Jiayu Yin, Ping Lin, Yanjie Li, Zixun Yang, Shumei Hu, Jin Wang, Baihui Zhang, Chenfeng Ji & Shoudong Guo
3. Department of Physiology, University of Alberta, T6G2R3, Edmonton, Canada
   Saloni Koshti
4. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 510220, Guangzhou, China
   Junfeng Wang

Authors

1. Ting Li
2. Jiayu Yin
3. Yubin Ji
4. Ping Lin
5. Yanjie Li
6. Zixun Yang
7. Shumei Hu
8. Jin Wang
9. Baihui Zhang
10. Saloni Koshti
11. Junfeng Wang
12. Chenfeng Ji
13. Shoudong Guo

Corresponding authors

Correspondence toJunfeng Wang, Chenfeng Ji or Shoudong Guo.

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Li, T., Yin, J., Ji, Y. et al. Setosphapyrone C and D accelerate macrophages cholesterol efflux by promoting LXRα/ABCA1 pathway.Arch. Pharm. Res. 43, 788–797 (2020). https://doi.org/10.1007/s12272-020-01255-w

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• Received: 16 January 2020
• Accepted: 22 July 2020
• Published: 10 August 2020
• Version of record: 10 August 2020
• Issue date: August 2020
• DOI: https://doi.org/10.1007/s12272-020-01255-w

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