Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro

BMC Complementary Medicine and Therapies

Research Article

Sumito Ogawa¹  Hiroko Sasakawa¹  Masahiro Akishita¹  Tatsuya Hosoi¹  Mitsutaka Yakabe¹ 

[1]Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7- 3-1, Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan

关键词: TJ-41;    Tail-suspension;    atrogin-1;    AMPK;    Herbal medicine;   

DOI  :  10.1186/s12906-022-03812-w

 received in 2020-12-06, accepted in 2022-11-28,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundMuscle disuse results in loss of skeletal muscle mass and function. Hochu-ekki-to (TJ-41; Bu-Zhong-Yi-Qi-Tang in Chinese) is an herbal medicinal formulation used to treat patients with frailty, fatigue and appetite loss. It has been suggested that two atrogenes, atrogin-1 and muscle Ring finger 1 (MuRF1), are ubiquitin ligases involved in disuse-induced muscle atrophy and that 5’ adenosine monophosphate-activated protein kinase (AMPK) is involved in skeletal muscle metabolism. Effects of TJ-41 on disuse-induced muscle atrophy are unclear.MethodsWe subjected differentiated C2C12 myotubes to serum starvation, then examined the effects of TJ-41 on atrogenes expression, AMPK activity and the morphology of the myotubes. Male C57BL/6J mice were subjected to tail-suspension to induce hindlimb atrophy. We administered TJ-41 by gavage to the control group and the tail-suspended group, then examined the effects of TJ-41 on atrogene expression, AMPK activity, and the muscle weight.ResultsSerum starvation induced the expression of atrogin-1 and MuRF1 in C2C12 myotubes, and TJ-41 significantly downregulated the expression of atrogin-1. Tail-suspension of the mice induced the expression of atrogin-1 and MuRF1 in skeletal muscle as well as its muscle atrophy, whereas TJ-41 treatment significantly downregulated the expression of atrogin-1 and ameliorated the loss of the muscle weight. In addition, TJ-41 also activated AMPK and inactivated Akt and mTOR in skeletal muscle in vivo.ConclusionTJ-41 inhibited atrogenes in an Akt-independent manner as well as activating AMPK in skeletal muscles in vivo, further implying the therapeutic potential of TJ-41 against disuse-induced muscle atrophy and other atrogenes-dependent atrophic conditions.

【 授权许可】

CC BY   
© The Author(s) 2022

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