Effects of herbal medicines on the muscle atrophy of sarcopenic mice.

Research Project

Project/Area Number	18K15383
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 52010:General internal medicine-related
Research Institution	The University of Tokyo
Principal Investigator	Yakabe Mitsutaka 東京大学, 医学部附属病院, 助教 (10747265)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	サルコペニア / 廃用性筋萎縮 / 補中益気湯 / 後肢懸垂モデルマウス / 筋萎縮関連因子 / AMPK / 漢方薬
Outline of Final Research Achievements	Muscle disuse results in loss of skeletal muscle mass and function in elderly individuals. Hochu-ekki-to (TJ-41) is an herbal medicinal formulation used to treat elderly patients. It has been suggested that two atrogenes, atrogin-1 and MuRF1, are ubiquitin ligases involved in disuse-induced muscle atrophy and AMPK is involved in skeletal muscle metabolism. Serum starvation induced the expression of atrogin-1 and MuRF1 in differentiated C2C12 myotubes, and TJ-41 significantly downregulated the expression of atrogin-1 and ameliorated the loss of myotube width. Male mice were subjected to tail-suspension to induce hindlimb atrophy, and administered TJ-41 by gavage. Tail-suspension induced the expression of atrogin-1 and MuRF1 in skeletal muscle as well as its muscle atrophy, whereas TJ-41 treatment downregulated the expression of atrogin-1 and ameliorated the loss of the muscle weight. TJ-41 also activated AMPK and inactivated Akt and mTOR in skeletal muscle in non-suspended mice.
Academic Significance and Societal Importance of the Research Achievements	本研究結果により、TJ-41が廃用性筋萎縮を抑制する新たなメカニズムが示唆された。サルコペニアやフレイルを有する高齢者に対しても、TJ-41が有効な可能性がある。高齢者医療において漢方は重要な位置を占めているがエビデンスは未だ不十分である。TJ-41をはじめとする漢方薬の作用メカニズムを明らかにすることで、高齢者の漢方薬使用のエビデンス確立の一助となることが期待される。