Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Antihepatotoxic effect of ethanol extracts from steam-dried ginseng berry on ᴅ-galactosamine/lipopolysaccharide-sensitized mice

ᴅ-galactosamine/lipopolysaccharide로 감작된 급성간독성 마우스 모델에서 인삼열매추출물의 간독성 개선 효과

  • Jang, Su Kil (College of Life Science, Gangneung-Wonju National University) ;
  • Park, Jun Sub (College of Life Science, Gangneung-Wonju National University) ;
  • Ahn, Jeong Won (College of Life Science, Gangneung-Wonju National University) ;
  • Jo, Boram (College of Life Science, Gangneung-Wonju National University) ;
  • Kim, Hyun Soo (College of Life Science, Gangneung-Wonju National University) ;
  • Kim, JeongHoon (College of Life Science, Gangneung-Wonju National University) ;
  • Kim, Sang Yun (College of Life Science, Gangneung-Wonju National University) ;
  • Park, Jung Youl (Department of Applied Chemistry, Daejeon University) ;
  • Lee, Do Ik (College of Pharmacy, Chung-Ang University) ;
  • Park, Hee Yong (College of Pharmacy, Chung-Ang University) ;
  • Joo, Seong Soo (College of Life Science, Gangneung-Wonju National University)
  • 장수길 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 박준섭 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 안정원 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 조보람 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 김현수 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 김정훈 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 김상윤 (강릉원주대학교 생명과학대학 생물의약신소재연구실) ;
  • 박정열 (대전대학교 응용화학과) ;
  • 이도익 (중앙대학교 약학대학 면역질환연구실) ;
  • 박희용 (중앙대학교 약학대학 면역질환연구실) ;
  • 주성수 (강릉원주대학교 생명과학대학 생물의약신소재연구실)
  • Received : 2017.07.17
  • Accepted : 2017.08.14
  • Published : 2017.12.31
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Abstract

The present study aimed to examine the hepatoprotective effects of ethanol extracts from steam-dried ginseng berry (SGBE) in both $\text\tiny{D}$-Galactosamine/Lipopolysaccharide ($\text\tiny{D}$-GalN/LPS)-sensitized mice and in vitro models. Our results clearly demonstrated that SGBE significantly reduced the level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase in blood, and $TNF{\alpha}$ was normalized in 8 h after the treatment with $\text\tiny{D}$-GalN/LPS. Coincidently, major organs remained unimpaired when compared to $\text\tiny{D}$-GalN/LPS control group. Moreover, p38, which stimulates expression of NAFLD-associated cytokines, was markedly inhibited when treated with SGBE. In vitro analysis revealed that the main components of SGBE, linoleic acid and ginsenoside Re/Rd, may play a role in protecting liver from $\text\tiny{D}$-GalN/LPS-induced toxicity. Finally, we concluded that SGBE may be a promising therapeutic agent for preventing damage to the liver.

생활 식습관의 변화와 비만은 성인성 대사질환 증가를 급속히 증가시켜왔고, 이에 따라 간내 지방축적으로 야기된 간염질환인 NAFLD의 유병률도 ~33%의 수준으로 높게 나타나고 있어 간경변증, 간세포암종을 포함한 간손상의 진행을 심각하게 고려해야 할 시점이다. 특히 알코올섭취와 관계없이 비만과 연계된 인슐린 저항성 간조직에서 지방간염과 간경화를 시작으로 간손상이 지속적으로 일어난다는 점에서 비교적 가벼운 간소견을 보이는 NAFLD라 할지라도 적극적인 치료의 대상으로 해야 한다. 본 연구에서 $\text\tiny{D}$-GalN/LPS로 유도된 급성간독성의 지표들(ALT, AST, ALP 및 LDH)이 SGBE 투여 시 유의한 수준으로 감소되어 효과적인 간 보호 효과가 입증되었으며 세포수준에서 NAFLD에서 높게 나타나는 염증성 사이토카인($TNF{\alpha}$, IL-6)의 발현이 현격히 억제되어 비만과 인슐린저항성으로 인한 간 내 지방의 침착으로 유발되는 NAFLD의 염증반응 조절이 예상된다. 특히 간 조직 H&E 염색 및 주요장기 비교분석에서 SGBE 투여 시 간 손상의 특징이 최소화 또는 정상소견을 나타냈을 뿐 아니라 주요장기(간, 비장, 신장 및 위)도 간 손상의 특징을 나타내지 않아 안전하게 사용할 수 있는 NAFLD 소재로 사용이 가능할 것으로 생각된다. 이와 같은 SGBE의 효능은 신호전달 단백질인 p38의 제어를 통해 NAFLD 유발 및 악화의 주된 cytokine인 $TNF{\alpha}$의 생성을 억제한 결과로 생각되며, 이는 SGBE에 포함된 linoleic acid 및 SGBE에 독특하게 높게 나타나는 ginsenoside Re 및 Rd가 주된 역할을 한 것으로 판단된다. 본 연구결과는 SGBE가 효과적인 간 보호 효능을 가지며 특히 비만과 인슐린저항성 질환(2형 당뇨 등)과 상관관계가 깊은 NAFLD에 유용한 보조치료법이 가능함을 제시하고 있어 간기능개선 및 보호 소재로서 개발이 기대된다.

Keywords

References

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