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조회496

김노수No Soo Kim

한국한의학연구원

Phytomedicine, Available online 3 September 2023, 155057 | https://doi.org/10.1016/j.phymed.2023.155057 Jakyak-gamcho-tang, a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, ameliorates dexamethasone-induced muscle atrophy and muscle dysfunction

Aeyung Kim ^a,¶, Yu Ri Kim ^b,¶, Sang-Min Park ^c,d,¶, Haeseung Lee ^c,e, Musun Park ^c, Jin-Mu Yi ^b, Seongwon Cha ^c, No Soo Kim ^b

^aKM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea

^bKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea

^cKM Data Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea

^dCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea

^eCollege of Pharmacy, Pusan National University, Busan 46241, Republic of Korea

^¶These authors contributed equally to this work.

Correspondence to: Seongwon Cha, Ph.D., No Soo Kim

Abstract

Background

Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, has long been used to relieve muscle tension and control muscle cramp-related pain. However, the effects of JGT on glucocorticoid-induced muscle atrophy are yet to be comprehensively clarified.

Purpose

The objective of the current study was to validate the protective effect of JGT in dexamethasone-induced muscle atrophy models and elucidate its underlying mechanism through integrated in silico – in vitro – in vivo studies.

Study design and Methods

Differential gene expression was preliminarily analyzed using the RNA-seq data to determine the effects of JGT on C2C12 myotubes. The protective effects of JGT were further validated in dexamethasone-treated C2C12 myotubes by assessing cell viability, myotube integrity, and mitochondrial function or in C57BL/6N male mice with dexamethasone-induced muscle atrophy by evaluating muscle mass and physical performance. Transcriptomic pathway analysis was also performed to elucidate the underlying mechanism.

Results

Based on preliminary gene set enrichment analysis using the RNA-seq data, JGT regulated various pathways related to muscle differentiation and regeneration. Dexamethasone-treated C2C12 myotubes and muscle tissues of atrophic mice displayed substantial muscle protein degradation and muscle loss, respectively, which was efficiently alleviated by JGT treatment. Importantly, JGT-mediated protective effects were associated with observations such as preservation of mitochondrial function, upregulation of myogenic signaling pathways, including protein kinase B/mammalian target of rapamycin/forkhead box O3, inhibition of ubiquitin-mediated muscle protein breakdown, and downregulation of inflammatory and apoptotic pathways induced by dexamethasone.

Conclusion

To the best of our knowledge, this is the first report to demonstrate that JGT could be a potential pharmaceutical candidate to prevent muscle atrophy induced by chronic glucocorticoid treatment, highlighting its known effects for relieving muscle spasms and pain. Moreover, transcriptomic pathway analysis can be employed as an efficient in silico tool to predict novel pharmacological candidates and elucidate molecular mechanisms underlying the effects of herbal medications comprising diverse biologically active ingredients.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-27)
연구진국내 연구진
분야 의약학 > 한의학

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