Journal of Nutrition and Health

  • 제57권1호
  • /
  • Pages.53-64
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  • 2024
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  • 2288-3886(pISSN)
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  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
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백지에서 추출한 oxypeucedanin hydrate의 미토콘드리아 기능 관련 근생성 효과

Effects of oxypeucedanin hydrate isolated from Angelica dahurica on myoblast differentiation in association with mitochondrial function

  • 송은주 (숙명여자대학교 식품영양학과) ;
  • 허지원 (숙명여자대학교 식품영양학과) ;
  • 장지희 (숙명여자대학교 생명시스템학부) ;
  • 권윤주 ( 한국한의약진흥원 한약소재개발센터) ;
  • 정윤희 (한국한의약진흥원 한약소재개발센터) ;
  • 김민정 (숙명여자대학교 생명시스템학부) ;
  • 김성은 (숙명여자대학교 식품영양학과)
  • Eun-Ju Song (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Ji-Won Heo (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Jee Hee Jang (Department of Biological Sciences, Sookmyung Women's University) ;
  • Yoon-Ju Kwon (Korean Medicine Material Development Center, National Institute for Korean Medicine Development) ;
  • Yun Hee Jeong (Korean Medicine Material Development Center, National Institute for Korean Medicine Development) ;
  • Min Jung Kim (Department of Biological Sciences, Sookmyung Women's University) ;
  • Sung-Eun Kim (Department of Food and Nutrition, Sookmyung Women's University)
  • 투고 : 2023.12.28
  • 심사 : 2024.02.07
  • 발행 : 2024.02.28
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초록

본 연구는 근생성 효능을 가진 천연화합물을 발굴하고자 oxypeucedanin hydrate가 근생성과 미토콘드리아에 미치는 영향 및 항암제 유도 미토콘드리아 손상에 대한 완화효과를 C2C12 근원세포와 zebrafish 모델을 통해 각각 확인하였다. 그 결과, oxypeucedanin hydrate는 다핵의 근관세포의 수와 분화말기 표지자인 Myh4의 발현량을 증가시켰고 근육단백질 분해 인자인 MuRF1과 MAFbx의 발현량은 감소시켰다. 또한 미토콘드리아 생합성 조절인자인 Pgc1α, Tfam과 전자전달계 구성인자인 Sdha, Cox1의 발현은 증가시키고, 미토콘드리아 융합인자인 Opa1의 발현 또한 증가시킴과 동시에 미토콘드리아 분열을 표지하는 Drp1의 발현은 감소시켰다. 한편 zebrafish 모델을 통해 항암제 유도 미토콘드리아 손상에 대한 개선효과를 확인한 결과, oxypeucedanin hydrate는 항암제에 의해 유도된 미토콘드리아 손상을 완화시켰다. 이상의 결과들은 oxypeucedanin hydrate가 미토콘드리아 기능 증진을 매개로 근원세포 분화 촉진 및 근육 단백질 분해 저하 효과를 나타냄을 시사한다. 따라서 본 연구를 통해 oxypeucedanin hydrate가 근생성 효과를 나타낼 수 있는 잠재적인 유효소재로서의 가능성을 제시하였다.

Purpose: Mitochondria play a crucial role in preserving skeletal muscle mass, and damage to mitochondria leads to muscle mass loss. This study investigated the effects of oxypeucedanin hydrate, a furanocoumarin isolated from Angelica dahurica radix, on myogenesis and mitochondrial function in vitro and in zebrafish models. Methods: C2C12 myotubes cultured in media containing 0.1, 1, 10, or 100 ng/mL oxypeucedanin hydrate were immunostained with myosin heavy chain (MHC), and then multinucleated MHC-positive cells were counted. The expressions of markers related to muscle differentiation, muscle protein degradation, and mitochondrial function were determined by quantitative reverse transcription polymerase chain reaction. To investigate the effects of oxypeucedanin hydrate on mitochondrial dysfunction, Tg(Xla.Eef1a1:mito-EGFP) zebrafish embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without oxypeucedanin hydrate and analyzed for mito-EGFP intensity and mitochondrial length. Results: Oxypeucedanin hydrate significantly increased MHC-positive multinucleated myotubes (≥ 3 nuclei) and increased the expression of the myogenic marker myosin heavy chain 4. However, it decreased the expressions of muscle-specific RING finger protein 1 and muscle atrophy f-box (markers of muscle protein degradation). Furthermore, oxypeucedanin hydrate enhanced the expressions of markers of mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, transcription factor a mitochondrial, succinate dehydrogenase complex flavoprotein subunit A, and cytochrome c oxidase subunit 1) and mitochondrial fusion (optic atrophy 1). However, it reduced the expression of dynamin-related protein 1 (a mitochondrial fission regulator). Consistently, oxypeucedanin hydrate reduced FOLFIRI-induced mitochondrial dysfunction in the skeletal muscles of zebrafish embryos. Conclusion: The study indicates that oxypeucedanin hydrate promotes myogenesis by improving mitochondrial function, and thus, suggests oxypeucedanin hydrate has potential use as a nutritional supplement that improves muscle mass and function.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2020R1C1C1007553, 2023R1A2C1005313 to Sung-Eun Kim, NRF-2022R1F1A1074668 to Min Jung Kim).

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