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Inhibitory Effect of Aged Black Platycodi Radix Extract on Expression and Activation of Matrix Metalloproteinases in Oxidative-stressed Melanoma Cells

쥐 흑색종 세포에서 산화적 스트레스에 의한 MMPs의 발현과 활성에 대한 흑도라지 추출물의 억제 효과

  • Chae, Yong-Byung (Department of Chemistry, Dong-Eui University) ;
  • Lee, Soo-Jin (Department of Chemistry, Dong-Eui University) ;
  • Jang, Ho-Jung (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Park, Jung-Ae (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Kim, Moon-Moo (Department of Chemistry, Dong-Eui University) ;
  • Chung, Kyung-Tae (Department of Clinical Laboratory Science and Blue-Bio Industry RIC, Dong-Eui University)
  • 채용병 (동의대학교 화학과) ;
  • 이수진 (동의대학교 화학과) ;
  • 장호정 (동의대학교 생명응용과학과) ;
  • 박정애 (동의대학교 생명응용과학과) ;
  • 김문무 (동의대학교 화학과) ;
  • 정경태 (동의대학교 임상병리학과 및 블루바이오 소재개발 및 실용화 지원 센터)
  • Received : 2010.02.18
  • Accepted : 2010.03.19
  • Published : 2010.05.31

Abstract

The root of Playtcodon grandiflorum, called Platycodi radix, has been a favorite edible plant in Asia and contains a large amount of saponins. Melanoma cells (B16F10) were used to investigate the inhibitory effect of aged black Platycodi radix extract (ABPRE) on oxidative stress and matrix metalloproteinases (MMPs). Platycodon radix has been known to have a variety of medicinal effects such as prevention of gastric ulcers, antiallergenic activities, histamine release inhibition, and antioxidant effects. However, the mechanism of its action remains unclear in humans. ABPRE was prepared using ethanol extraction of aged black Platycodi radix. In an antioxidant effect study of ABPRE, it was observed that ABPRE specifically exhibited the scavenging activity of DPPH radical, but did not inhibit the production of malondialdehyde from lipid peroxidation. DNA oxidation was also blocked in the presence of ABPRE. In addition, ABPRE decreased the expression and activation of MMP-2 stimulated by phenazine methosulfate. Furthermore, ABPRE revealed the inhibitory effect on melanin production induced by L-dopa via antioxidant effect and the reduction of tyrosinase expression. Especially, the expression of antioxidant enzymes such as SOD-1 and SOD-2 regulated by Nrf2 was increased in the presence of ABPRE. Therefore, it appears that ABPRE may be a possible chemopreventive agent for the prevention of metastasis related to oxidative stress.

도라지는 민간에서 항궤양, 항진통, 항알러지, 혈관과 히스타민 억제 및 항산화 효과가 있는 것으로 알려져 있고, 그 뿌리인 길경은 아시아에서 식용으로 즐겨먹는 식품 소재로 사포닌이 과량 함유되어 있는 것으로 보고 되어 있으나, 그 작용기전은 과학적으로 해명되지 않았다. 본 연구에서 처음으로 흑도라지가 특정한 공정기술을 이용하여 개발되었으며, 산화적 스트레스 및 MMPs) 대한 ABPRE의 억제 효과를 조사하였다. ABPRE의 항산화효과를 조사하기 위해서 DPPH radical, hydroxyl radical, reducing power, hydrogen peroxide, lipid peroxidation 및 DNA 산화에 대한 연구를 수행하였다. 연구 결과 ABPRE는 DPPH radical 소거에는 효과를 나타내었으나 지질과산화에 의한 malondialdehyde의 생성은 억제하지 않았다. 그러나, ABPRE의 존재 하에서 산화적 DNA 손상이 억제되었다. 또한 gelatin zymography 및 western blot 분석에서 ABPRE는 PMS (phenazine methosulfate)에 의해서 자극된 MMP-2의 발현과 활성을 감소시켰으며, ABPRE는 항산화 효과 및 tyrosinase 발현 억제에 의한 L-DOPA로 유발된 melanin 생성을 저해 하였을 뿐만 아니라 Nrf2에 의해서 조절되는 항산화 효소인 SOD-1과 SOD-2의 발현을 증가시키는 것으로 나타났다. 그러므로 ABPRE는 항산화와 관련 있는 암전이의 예방을 위한 항암제의 후보 소재로 그 가능성이 기대된다.

Keywords

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