Cited by 64Muscle Physiology and DisordersMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

Dihydromyricetin Attenuates Dexamethasone-Induced Muscle Atrophy by Improving Mitochondrial Function Via the PGC-1α Pathway

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Huang, Yujie, Chen, Ka, Ren, Qingbo, Yi, Long, Zhu, Jundong, Zhang, Qianyong, Mi, Mantian·2018·Cellular Physiology and Biochemistry

Abstract

BACKGROUND/AIMS: Skeletal muscle atrophy is an important health issue and can impose tremendous economic burdens on healthcare systems. Glucocorticoids (GCs) are well-known factors that result in muscle atrophy observed in numerous pathological conditions. Therefore, the development of effective and safe therapeutic strategies for GC-induced muscle atrophy has significant clinical implications. Some natural compounds have been shown to effectively prevent muscle atrophy under several wasting conditions. Dihydromyricetin (DM), the most abundant flavonoid in Ampelopsis grossedentata, has a broad range of health benefits, but its effects on muscle atrophy are unclear. The purpose of this study was to evaluate the effects and underlying mechanisms of DM on muscle atrophy induced by the synthetic GC dexamethasone (Dex). METHODS: The effects of DM on Dex-induced muscle atrophy were assessed in Sprague-Dawley rats and L6 myotubes. Muscle mass and myofiber cross-sectional areas were analyzed in gastrocnemius muscles. Muscle function was evaluated by a grip strength test. Myosin heavy chain (MHC) content and myotube diameter were measured in myotubes. Mitochondrial morphology was observed by transmission electron microscopy and confocal laser scanning microscopy. Mitochondrial DNA (mtDNA) was quantified by real-time PCR. Mitochondrial respiratory chain complex activities were examined using the MitoProfile Rapid Microplate Assay Kit, and mitochondrial membrane potential was assessed by JC-1 staining. Protein levels of mitochondrial biogenesis and dynamics markers were detected by western blotting. Myotubes were transfected with siRNAs targeting peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM) and mitofusin-2 (mfn2) to determine the underlying mechanisms. RESULTS: In vivo, DM preserved muscles from weight and average fiber cross-sectional area losses and improved grip strength. In vitro, DM prevented the decrease in MHC content and myotube diameter. Moreover, DM stimulated mitochondrial biogenesis and promoted mitochondrial fusion, rescued the reduced mtDNA content, improved mitochondrial morphology, prevented the collapse in mitochondrial membrane potential and enhanced mitochondrial respiratory chain complex activities; these changes restored mitochondrial function and improved protein metabolism, contributing to the prevention of Dex-induced muscle atrophy. Furthermore, the protective effects of DM on mitochondrial function and muscle atrophy were alleviated by PGC-1α siRNA, TFAM siRNA and mfn2 siRNA transfection in vitro. CONCLUSION: DM attenuated Dex-induced muscle atrophy by reversing mitochondrial dysfunction, which was partially mediated by the PGC-1α/TFAM and PGC-1α/mfn2 signaling pathways. Our findings may open new avenues for identifying natural compounds that improve mitochondrial function as promising candidates for the management of muscle atrophy.

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Crossref · 10.1159/000493040

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  • Ampelopsin administered for 14 days significantly attenuates dexamethasone-induced muscle atrophy in SD rats by reversing mitochondrial dysfunction, partially mediated by the PGC-1α/Tfam and PGC-1α/mitofusin-2 signaling pathway.

    “Moreover, ampelopsin administered for 14 days significantly attenuates dexamethasone-induced muscle atrophy in SD rats by reversing mitochondrial dysfunction, which was partially mediated by the PGC-1α/mitochondrial transcription factor A (Tfam) and PGC-1α/mitofusin-2 signaling pathway [124].”

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Authors
Huang, Y., Chen, K., Ren, Q., Yi, L., Zhu, J., Zhang, Q., & Mi, M.
Affiliations
Army Medical University (CN)
Venue
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Published
2018
Volume
49
Issue
2
Pages
758-779
ISSN
  • 1015-8987 (ISSN-L)
  • 1421-9778
OpenAlex
W2889179762
Cited by
64
References
84
Citations by year
2026: 8 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 6 · 2018: 1
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Cellular Physiology and Biochemistry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
dihydromyricetin, dexamethasone, glucocorticoid-induced muscle atrophy, skeletal muscle atrophy, PGC-1α, mitochondrial biogenesis, mitochondrial fusion, mitochondrial dynamics, mitochondrial function, mitochondrial DNA, myofiber cross-sectional area, grip strength, myosin heavy chain, TFAM, mitofusin 2, natural flavonoids
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Dexamethasone, DNA, Mitochondrial, Male, Membrane Proteins, Mitochondria, Muscular Atrophy, Transcription Factors, Signal Transduction, Rats, Sprague-Dawley, GTP Phosphohydrolases, Mitochondrial Proteins, ATP Synthetase Complexes, Myoblasts, RNA Interference, RNA, Small Interfering, Flavonols, Protein Carbonylation, Voltage-Dependent Anion Channel 1, Rats, Membrane Potential, Mitochondrial

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