Journal of Nutrition and Health

  • 제51권4호
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  • Pages.275-286
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  • 2018
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  • 2288-3886(pISSN)
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  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
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제조방법에 따른 떫은감 (Diosyros kaki Thumb.)의 대사체 프로파일링과 중성지질/콜레스테롤 대사 관련 유전자발현 연구 : in vitro 및 in vivo 연구

Metabolites profiling and hypolipidemic/hypocholesterolemic effects of persimmon (Diosyros kaki Thumb.) by different processing procedures: in vitro and in vivo studies

  • 박수연 (이화여자대학교 식품영양학과) ;
  • 오은경 (이화여자대학교 식품영양학과) ;
  • 임예니 (이화여자대학교 식품영양학과) ;
  • 신지윤 (이화여자대학교 임상보건융합대학원) ;
  • 정희아 (차의과학대학교 식품생명공학과) ;
  • 박송이 (차의과학대학교 식품생명공학과) ;
  • 이진희 (차의과학대학교 식품생명공학과) ;
  • 최정숙 (농촌진흥청 국립농업과학원 농식품자원부) ;
  • 권오란 (이화여자대학교 식품영양학과)
  • Park, Soo-Yeon (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Oh, Eun-Kyung (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Lim, Yeni (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Shin, Ji-Yoon (Ewha Graduate School of Converging Clinical&Public Health) ;
  • Jung, Hee-Ah (Department of Food Science and Biotechnology, CHA University) ;
  • Park, Song-Yi (Department of Food Science and Biotechnology, CHA University) ;
  • Lee, Jin Hee (Department of Food Science and Biotechnology, CHA University) ;
  • Choe, Jeong-Sook (Department of Agrofood Resources, Rural Development Administration National Institute of Agricultural Sciences) ;
  • Kwon, Oran (Department of Nutritional Science and Food Management, Ewha Womans University)
  • 투고 : 2018.06.18
  • 심사 : 2018.07.09
  • 발행 : 2018.08.31
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초록

본 연구는 떫은감 청도반시의 분말을 열수 추출하고 칼럼 추출하는 과정에서 획득한 PWE와 TEP에 대한 대사체 프로파일을 분석하고, 유리지방산을 처리한 HepG2 세포와 식이로 고지혈증을 유도한 Wistar계 흰쥐의 간조직을 사용하여 중성지질 및 콜레스테롤 대사 관련 유전자 발현을 측정하였다. 대사체 분석은 가스크로마토그래프-질량분석법과 액체크로마토그래프-질량분석법을 사용하였으며, PLS-DA 분석과 heatmap 분석을 실시한 결과 PWE는 떫은감 분말과 비교적 유사한 대사체 프로파일을, 그리고 TEP는 떫은감 분말과 매우 다른 대사체 프로파일을 가지고 있음을 확인하였다. 세포실험과 또한 세포실험에서 얻어진 결과를 검증하기 위해 수행된 동물실험에서 PWE와 TEP는 모두 SREBP1c와 FAS 유전자 발현을 감소하여 간의 지방축적을 감소시키는 것으로 관찰되었으나, 콜레스테롤 축적을 억제하는 효능은 PWE에 비해 TEP에서 우세하게 증가하는 것이 관찰되었다. 특별히 TEP는 SREBP2, HMGCR 유전자 발현을 억제하고 LDLR 유전자 발현을 촉진하는 것으로 나타났다. TEP는 탄닌 중 Gallic acid 그리고 장쇄지방산아미드인 Oleamide와 Palmitamide 함량이 유의하게 증가되었으므로, 향후 이들 성분과 타깃 유전자의 상관성을 분석하고, 이를 통해 시스템네트워크로 나타내어 대사체 프로파일에 따른 지질 및 콜레스테롤 대사 간 상호 영향을 추가적으로 연구해야 할 것으로 사료된다.

Purpose: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). Methods: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. Results: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. Conclusion: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

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피인용 문헌

  1. Bioactivities of Phenolic Compounds from Kiwifruit and Persimmon vol.26, pp.15, 2021, https://doi.org/10.3390/molecules26154405