Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model

  • Hyo-Jin Kim (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Seon Kyeong Park (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Soo Hyun Park (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Yu Geon Lee (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Jae-Ho Park (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Jin-Taek Hwang (Personalized Diet Research Group, Korea Food Research Institute) ;
  • Min-Yu Chung (Department of Food and Nutrition, Gangseo University)
  • Received : 2023.06.28
  • Accepted : 2023.10.12
  • Published : 2024.02.28
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Abstract

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Keywords

Acknowledgement

This study was supported by the Main Research Program of the Korea Food Research Institute (KFRI) and was funded by the Ministry of Science and ICT (E0210601-03).

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