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Planta Med 2023; 89(05): 484-492
DOI: 10.1055/a-1891-3366
Biological and Pharmacological Activity
Original Papers

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy

Hyejin Lee
1   Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Womenʼs University, Seoul, Korea
,
Ji Hye Jeong
1   Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Womenʼs University, Seoul, Korea
,
Seung Hwan Hwang
2   R & D Center, Huons Co., Ltd., Gyeonggi-Do, Korea
,
Sung Hum Yeon
2   R & D Center, Huons Co., Ltd., Gyeonggi-Do, Korea
,
Jae-Ha Ryu
1   Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Womenʼs University, Seoul, Korea
› Author AffiliationsSupported by: National Research Foundation of Korea NRF-2021R1I1A1A01052160
Supported by: Korean Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) IPET-121016031SB010
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Abstract

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((−)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica. C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage, showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF-κB signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type II a, II b, and II x), known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss.

Key words

Alnus japonica - Betulaceae - myogenesis - muscle atrophy - muscle fiber - C2C12


Publication History

Received: 27 January 2022

Accepted after revision: 04 July 2022

Accepted Manuscript online:
04 July 2022

Article published online:
05 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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