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플라보노이드 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색

Screening of Flavonoid Compounds with HMG-CoA Reductase Inhibitory Activities

  • 손건호 (안동대학교 생활과학대학 식품영양학과) ;
  • 이주연 (안동대학교 생활과학대학 식품영양학과) ;
  • 이정순 (경상북도산림자원개발원) ;
  • 강삼식 (서울대학교 천연물과학연구소) ;
  • 손호용 (안동대학교 생활과학대학 식품영양학과) ;
  • 권정숙 (안동대학교 생활과학대학 식품영양학과)
  • Son, Kun Ho (Department of Food Science and Nutrition, Andong National University) ;
  • Lee, Ju Yeon (Department of Food Science and Nutrition, Andong National University) ;
  • Lee, Jeong Soon (Forest Resources Development Institute of Gyeongsangbuk-do) ;
  • Kang, Sam Sik (Natural Products Research Institute, Seoul National University) ;
  • Sohn, Ho Yong (Department of Food Science and Nutrition, Andong National University) ;
  • Kwon, Chong Suk (Department of Food Science and Nutrition, Andong National University)
  • 투고 : 2017.11.08
  • 심사 : 2018.01.16
  • 발행 : 2018.02.28

초록

심혈관계 질환은 질환별 사망률 순위에 있어서 세계에서는 1위이며, 우리나라에서는 2위인 질병이다. 심혈관계 질환 발생의 주 위험 요인인 콜레스테롤은 HMG-CoA reductase에 의해 간에서 신생합성이 조절된다. 현재 고콜레스테롤혈증 치료에 statin이 널리 사용되고 있지만 광범위한 부작용이 보고되고 있어서 이를 대체하거나 보조할 수 있는 천연물 유래의 기능성 물질 개발이 필요한 실정이다. 따라서 본 연구에서는 혈장 콜레스테롤 감소 활성을 가지는 물질을 발굴하고자 98종의 플라보노이드 및 그와 관련된 화합물들을 대상으로 $10{\mu}g/ml$ 농도에서 HMG-CoA reductase 저해 활성을 탐색하였다. 그 결과, sophoraflavanone G, morin, 및 kuraridin이 각각 54.6%, 45.04% 및 21.9%의 저해활성을 타내었으며, $IC_{50}$값을 계산한 결과, sophoraflavanone G가 $7.3{\mu}g/ml$로 가장 낮았으며 morin과 kuraridin은 각각 $13.3{\mu}g/ml$$87.4{\mu}g/ml$으로 확인되어, 향후 고콜레스테롤혈증 예방 및 치료제의 가능성을 제시하였다.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

키워드

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