Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9

  • Authors:
    • Huihui Li
    • Jun Li
    • Xianjing Zhang
    • Jiaomeng Li
    • Cong Xi
    • Wenqiong Wang
    • Youli Lu
    • Lijiang Xuan
  • View Affiliations

  • Published online on: September 28, 2021     https://doi.org/10.3892/etm.2021.10817
  • Article Number: 1381
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Abstract

Our previous study identified euphornin L as an active lipid-lowering compound in high-fat diet-fed Golden Syrian hamsters. The aim of the present study was to investigate the mechanisms underlying the lipid-lowering effects of euphornin L. Euphornin L in HepG2 cells was assessed via DiI-LDL update assays and found to increase LDL-update and LDLR protein levels. RNA interference assays demonstrated that its LDL-update effects were LDLR-dependent. Dual luciferase reporter and mRNA stability assays revealed that euphornin L had little effect on LDLR mRNA transcription but lengthened the half-life of LDLR mRNA by activating ERK protein in cells. Euphornin L decreased the secretion of PCSK9 protein and alleviated PCSK9-mediated LDLR protein degradation. In vivo experiments in hamsters, which were treated with euphornin L (30 mg/kg/day) for 3 weeks, confirmed these findings. LDLR protein levels in liver tissue were upregulated, while PCSK9 protein levels in serum were downregulated. Altogether, the present study demonstrated that euphornin L increased LDLR protein levels by dual regulation of LDLR mRNA and PCSK9 protein, and represented an active compound for lipid-lowering drug development.
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December-2021
Volume 22 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Li H, Li J, Zhang X, Li J, Xi C, Wang W, Lu Y and Xuan L: Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9. Exp Ther Med 22: 1381, 2021
APA
Li, H., Li, J., Zhang, X., Li, J., Xi, C., Wang, W. ... Xuan, L. (2021). Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9. Experimental and Therapeutic Medicine, 22, 1381. https://doi.org/10.3892/etm.2021.10817
MLA
Li, H., Li, J., Zhang, X., Li, J., Xi, C., Wang, W., Lu, Y., Xuan, L."Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9". Experimental and Therapeutic Medicine 22.6 (2021): 1381.
Chicago
Li, H., Li, J., Zhang, X., Li, J., Xi, C., Wang, W., Lu, Y., Xuan, L."Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1381. https://doi.org/10.3892/etm.2021.10817