Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Inhibitory Effects of Litsea japonica Flesh Water Extract against Endoplasmic Reticulum Stress in HepG2 Cells

HepG2 세포에서 까마귀쪽나무 과육 열수 추출물의 소포체 스트레스 억제 효능

  • 김은옥 (대구한의대학교 한의과대학) ;
  • 제갈경환 (대구한의대학교 한의과대학) ;
  • 김재광 (대구한의대학교 한의과대학) ;
  • 이주상 (제주한의학연구원) ;
  • 박정아 (대구한의대학교 한의과대학) ;
  • 김상찬 (대구한의대학교 한의과대학) ;
  • 조일제 (대구한의대학교 한의과대학)
  • Received : 2018.09.21
  • Accepted : 2018.10.17
  • Published : 2018.11.30
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Abstract

Objectives : Endoplasmic reticulum (ER) stress designates cellular responses to the accumulation of misfolded and unfolded proteins in ER, which is related to a variety of liver diseases. Present study investigated the inhibitory effects of Litsea japonica flesh water extract (LJE) aganist ER stress. Methods : After HepG2 cells were pretreated with LJE and subsequently exposed to tunicamycin (Tm) or thapsigargin (Tg), expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 kDa (GRP78), asparagine synthetase (ASNS), and endoplasmic reticulum DnaJ homologue 4 (ERDJ4) were determined by immunoblot and real-time PCR analysis. Three canonical signaling pathways in response to ER stress were examined to explore molecular mechanisms involved. Results : Pretreatment of 1 mg/mL LJE inhibited Tm- or Tg-induced CHOP expression, while L. japonica fruit water extract did not. In addition, LJE decreased the levels of GRP78, ASNS, and ERDJ4 mRNA by Tm. Moreover, phosphorylations of eukaryotic translation initiation factor $2{\alpha}$ and inositol-requiring enzyme 1, expression of nuclear form of activating transcription factor $6{\alpha}$, and transactivation of ER stress response element- and unfolded protein response element-harboring luciferase activities were inhibited by LJE pretreatment. Conclusions : Present results suggest that LJE would be a candidate to prevent or treat ER stress-mediated liver injuries.

Keywords

HBBJBB_2018_v26n4_307_f0001.png 이미지

Figure 1. The effect of L. japonica water extract on ER stress-mediated CHOP expression.

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Figure 2. The effect of LJE on ER stress-dependent target genes expression.

HBBJBB_2018_v26n4_307_f0003.png 이미지

Figure 3. The effect of LJE on Tm-mediated UPR signaling pathway.

HBBJBB_2018_v26n4_307_f0004.png 이미지

Figure 4. The effect of LJE on ERSE- and UPRE-luciferase activity by Tm.

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