Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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A Mixture of Morus alba and Angelica keiskei Leaf Extracts Improves Muscle Atrophy by Activating the PI3K/Akt/mTOR Signaling Pathway and Inhibiting FoxO3a In Vitro and In Vivo

  • Hyun Hwangbo (Anti-Aging Research Center, Dong-eui University) ;
  • Min Yeong Kim (Anti-Aging Research Center, Dong-eui University) ;
  • Seon Yeong Ji (Anti-Aging Research Center, Dong-eui University) ;
  • Da Hye Kim (Anti-Aging Research Center, Dong-eui University) ;
  • Beom Su Park (Anti-Aging Research Center, Dong-eui University) ;
  • Seong Un Jeong (Hamsoa Pharmaceutical Co., Ltd.) ;
  • Jae Hyun Yoon (Hamsoa Pharmaceutical Co., Ltd.) ;
  • Tae Hee Kim (Hamsoa Pharmaceutical Co., Ltd.) ;
  • Gi-Young Kim (Department of Marine Life Science, Jeju National University) ;
  • Yung Hyun Choi (Anti-Aging Research Center, Dong-eui University)
  • Received : 2023.06.07
  • Accepted : 2023.08.08
  • Published : 2023.12.28
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Abstract

Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and myogenin) and decreased the expression levels of E3 ubiquitin ligases (atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

Keywords

Acknowledgement

This study was supported by the Technology Development Program (S3149070) funded by the Ministry of SMEs and Startups (MSS, Korea). The authors would like to thank Core-Facility Center for Tissue Regeneration, Dong-eui University (Busan, Korea), for letting us use their flow cytometer and fluorescence microscope.

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