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Chrysin attenuates diabetic sarcopenia by regulating myogenic transcription factors and reducing muscle degradation in high glucose-exposed C2C12 cells and a type 2 diabetes animal model

Chrysin의 고농도 포도당에 노출된 C2C12 세포와 제2형 당뇨병 동물모델에서 근육전사 인자 조절 및 근육분해 완화를 통한 당뇨병성 근감소증 억제 효과

  • Dong Yeon Kim (Department of Food Science and Nutrition, Andong National University) ;
  • Min-Kyung Kang (Department of Food Science and Nutrition, Andong National University)
  • 김동연 (국립안동대학교 식품영양학과) ;
  • 강민경 (국립안동대학교 식품영양학과)
  • Received : 2024.10.06
  • Accepted : 2024.10.17
  • Published : 2024.10.31

Abstract

Purpose: Sarcopenia is defined as the age-related loss of muscle mass and strength. Although the etiology, pathogenesis, and diagnosis of sarcopenia are not completely understood, diabetes has been implicated in the development of frailty and functional impairment associated with sarcopenia. This study examined the relationship between diabetes and sarcopenia and explored the efficacy of chrysin, a natural flavonoid found in honey and propolis, as a preventive agent for diabetic sarcopenia. Methods: A mouse myoblast cell line (C2C12) was incubated in media containing 5.5 mM glucose or 33 mM glucose (high glucose) with or without 20 µM chrysin for up to seven days. In addition, a type 2 diabetic animal model, db/db mice, was administered chrysin (10 mg/kg/day) orally for 10 weeks. The protein levels were quantified using western blot analysis with antibodies targeting specific myogenic transcription factors, such as MyoD, myogenin, and Myf5, as well as proteins associated with muscle protein degradation, including Murf1, Atrogin1, and myostatin. Results: Hyperglycemia downregulated the expression of myogenic transcription factors (MyoD, myogenin, and Myf5) and proteins that regulate muscle degradation (Murf1 and Atrogin1) in C2C12 cells treated with high glucose and db/db mice. The chrysin treatment counteracted these effects, promoting the expression of these factors. These results suggest that chrysin can regulate muscle protein turnover and prevent muscle atrophy in diabetic sarcopenia. Conclusion: Chrysin has potential as a bioactive ingredient in preventing diabetic sarcopenia.

본 연구에서는 고농도에 노출된 근육세포와 제2형 당뇨병 동물모델을 활용하여 당뇨병으로 인한 근감소증을 완화시키는 chrysin의 효능에 대해 알아보고자 하였다. C2C12세포를 이용하여 고농도의 포도당에 노출시켰을 때 근세포 분화에 관여하는 전사인자들의 발현 근 지연됨으로써 근세포의 분화를 조절 및 근육분해 완화 효과 또한 chrysin을 처리하였을 때 분화된 myotube를 보호하는 단백질의 발현이 개선됨을 확인하였다. 또한 제2형 당뇨병 동물모델인 db/db 마우스에 10 mg/kg 농도로 10주간 chrysin을 투여하였을 때 근육의 양이 유의하게 보호되는 것을 확인하였으며 근육의 분화에 관여하는 단백질의 발현을 개선하고, 고혈당에 의한 근위축을 억제함으로써 당뇨병성 근감소증을 개선시키는 효능을 나타내는 것을 확인하였다. 따라서 chrysin은 고혈당으로 유도된 당뇨병성 근감소증을 예방하는 기능성 성분으로 서의 활용 가능성을 제시하였다.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2021R1I1A0104231612, 2022R1I1A1A01067661 and 2017R1A6A3A04011473).

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