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A Chalcone from Ashitaba (Angelica keiskei) Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy

1
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women’s University, 100 Chungparo 47-Gil, Yongsan-Gu, Seoul 04310, Korea
2
Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea
3
Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
*
Authors to whom correspondence should be addressed.
Minson Kweon and Hyejin Lee contributed equally to this work.
Nutrients 2019, 11(10), 2419; https://doi.org/10.3390/nu11102419
Received: 20 September 2019 / Revised: 30 September 2019 / Accepted: 5 October 2019 / Published: 10 October 2019
Ashitaba, Angelica keiskei Koidzumi (AK), as a traditional medicine in Korea, Japan, and China, has been known as an elixir of life having therapeutic potential. However, there is no scientific evidence to support that Ashitaba can enhance or maintain muscle strength. To find a new therapeutic agent from the medicinal plant, we evaluated the anti-myopathy effect of chalcones from ethanol extract of AK (EAK) in cellular and animal models of muscle atrophy. To examine anti-myopathy activity, EAK was treated into dexamethasone injected rats and muscle thickness and histopathological images were analyzed. Oral administration of EAK (250 or 500 mg/kg) alleviated muscle atrophic damages and down-regulated the mRNA levels of muscle-specific ubiquitin-E3 ligases. Among ten compounds isolated from EAK, 4-hydroxyderricin was the most effective principle in stimulating myogenesis of C2C12 myoblasts via activation of p38 mitogen-activated protein kinase (MAPK). In three cellular muscle atrophy models with C2C12 myoblasts damaged by dexamethasone or cancer cell-conditioned medium, 4-hydroxyderricin protected the myosin heavy chain (MHC) degradation through suppressing expressions of MAFbx, MuRF-1 and myostatin. These results suggest that the ethanol extract and its active principle, 4-hydroxyderricin from AK, can overcome the muscle atrophy through double mechanisms of decreasing muscle protein degradation and activating myoblast differentiation. View Full-Text
Keywords: Ashitaba; Angelica keiskei; 4-hydroxyderricin; myogenesis; muscle atrophy Ashitaba; Angelica keiskei; 4-hydroxyderricin; myogenesis; muscle atrophy
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Kweon, M.; Lee, H.; Park, C.; Choi, Y.H.; Ryu, J.-H. A Chalcone from Ashitaba (Angelica keiskei) Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy. Nutrients 2019, 11, 2419.

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