Glabridin Inhibits Dexamethasone-Induced Muscle Atrophy
Abstract
Prevention of muscle wasting is known to contribute to improving the quality of life and extending a healthy life. Recently, we have reported that licorice flavonoid oil containing glabridin, which is a prenylated isoflavone, enhances muscle mass in mice. In this study, we investigated the prevention effect of glabridin on dexamethasone-induced muscle atrophy and clarified its mechanism in cultured myotubes and in muscle of mice. Treatment with glabridin to C2C12 myotubes inhibited dexamethasone-induced protein degradation through dexamethasone-induced expression of ubiquitin ligases, MuRF1 and Cbl-b, but not atrogin-1. Mechanistically, glabridin inhibited nuclear translocation of the glucocorticoid receptor. Glabridin directly bound to the glucocorticoid receptor, resulting in the inhibition of binding between dexamethasone and the receptor protein. Glabridin also inhibited dexamethasone-induced phosphorylation of p38 and FoxO3a, as the upstream for the induction of ubiquitin ligases in C2C12 myotubes. Moreover, the glabridin-induced inhibition of protein degradation was eliminated by knockdown of the glucocorticoid receptor, but not by p38 knockdown. These data indicated that the inhibitory mechanism of glabridin against dexamethasone-induced muscle atrophy was mainly mediated by the inhibition of binding between dexamethasone and the glucocorticoid receptor in myotubes. Oral administration of glabridin prevented dexamethasone-induced protein degradation in the tibialis anterior muscle of mice. It was confirmed that glabridin inhibited dexamethasone-induced nuclear translocation of the glucocorticoid receptor and phosphorylation of FoxO3a in the muscle of mice. These findings suggest that glabridin is an effective food ingredient for the prevention of glucocorticoid-induced skeletal muscle atrophy.
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Glabridin inhibits dexamethasone-induced protein degradation via downregulating the expression of MuRF1 in C2C12 myotubes.
“Glabridin, a major bioactivity compound in licorice derived from the dried roots and rhizomes of Glycyrrhiza genus plants and used in both foods and traditional herbal medicine, inhibits dexamethasone-induced protein degradation via downregulating the expression of MuRF1 in C2C12 myotubes [97].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [97]
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Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy
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- Authors
- Yoshioka, Y., Kubota, Y., Samukawa, Y., Yamashita, Y., & Ashida, H.
- Affiliations
- Kobe University (JP)
- Corresponding author
- Ashida, Hitoshi
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 664
- Pages
- 157-166
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2913663303
- Cited by
- 54
- References
- 50
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 1
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cross-ministerial Strategic Innovation Promotion Program
- JSPS KAKENHI (17H00818)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Effects of Natural Compounds
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- glabridin, dexamethasone, muscle atrophy, glucocorticoid-induced muscle wasting, glucocorticoid receptor, ubiquitin ligase, MuRF1, Cbl-b, atrogin-1, protein degradation, p38 MAPK, FOXO3, licorice flavonoids, prenylated isoflavones, skeletal muscle, tibialis anterior, food ingredients
- MeSH terms
- Forkhead Box Protein O3, Animals, Cell Line, Dexamethasone, Isoflavones, Male, Mice, Inbred C57BL, Muscular Atrophy, Phenols, Receptors, Glucocorticoid, Signal Transduction, Muscle, Skeletal, p38 Mitogen-Activated Protein Kinases, Mice
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