Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Ethanol Extracts of Rheum undulatum and Inula japonica Protect Against Oxidative Damages on Human Keratinocyte HaCaT cells through the Induction of ARE/NRF2-dependent Phase II Cytoprotective Enzymes

종대황과 선복화 에탄올 추출물의 인간 피부 세포주인 HaCaT 세포에서 NRF2/ARE에 의존적인 유전자 발현의 유도를 통한 항산화 효과

  • Received : 2016.09.28
  • Accepted : 2017.03.12
  • Published : 2017.03.30
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Abstract

Mammalian cells control cellular homeostasis using a variety of defensive enzymes in order to combat against environmental oxidants and electrophiles. NF-E2-related factor-2 (NRF2) is a transcription factor that, in response to an exposure to oxidative stress, translocates into the nucleus and modulates the inducible expression of various phase II cytoprotective enzymes by binding to the antioxidant response element (ARE). In the present study, we have acquired 400 ethanol extracts of traditional medicinal plants and attempted to find out possible extract(s) that can increase the NRF2/ARE-dependent gene expression in human keratinocytes. As a result, we have identified that ethanol extracts of Rheum undulatum and Inula japonica strongly activated the ARE-dependent luciferase activity in HaCaT- ARE-luciferase cells. Exposure of ethanol extracts of Rheum undulatum and Inula japonica increased the viability and activated transcription and translation of NRF2-dependent phase II cytoprotective enzymes in HaCaT cells, such as heme oxygenase-1 (HO-1) and NAD[P]H:quinone oxidorecutase-1 (NQO1). In addition, ethanol extracts of Rheum undulatum and Inula japonica suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced generation of intracellular reactive oxygen species (ROS), thereby inhibiting the formation of 8-hydroxyguanosine (8-OHG) and 4-hydroxynonenal (4-HNE) in HaCaT cells. Together, our results demonstrate that ethanol extracts of Rheum undulatum and Inula japonica exert anti-oxidant effects via the induction of NRF2/ARE-dependent gene expression in human keratinocytes.

본 연구진은 HaCaT-ARE-luciferase 세포를 이용하여 400 여개의 약용식물 에탄올 추출물 중 NRF2/ARE 유도효과가 있는 신규 추출물을 검색하였고 이를 통하여 종대황(Rheum undulatum)과 선복화(Inula japonica)의 주정 추출물이 HaCaT-ARE-luciferase 세포에서 ARE 활성을 강하게 유도하는 것을 관찰하였다. 종대황과 선복화 에탄올 추출물은 HaCaT 세포에서 생존(viability)을 증가시켰고 NRF2/ARE에 의존적인 phase II cytoprotective 효소인 heme oxygenase-1 (HO-1)와 NADPH:quinone oxidoreductase-1 (NQO1)의 전사 및 단백질 발현을 강하게 유도하였다. 또한 종대황과 선복화 추출물은 HaCaT 세포에서 TPA로 유도한 세포 내 활성 산소 및 이를 통하여 생성되는 스트레스 마커인 8-hydroxydeoxyguanosine (8-OH-dG)과 4-hydroxynonenal (4HNE)의 발생을 강하게 억제하였다. 본 연구는 종대황과 선복화의 에탄올 추출물이 인간 피부 세포주인 HaCaT 세포에서 NRF2/ARE에 의존적인 유전자 발현의 유도를 통하여 강력한 항산화 효과를 발휘한다는 것을 증명한다.

Keywords

References

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