Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes
Open accessAbstract
Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity. These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy.
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Apigenin prevents LPS-induced atrogin-1 expression in C2C12 myotubes by regulating phosphorylation of JNK.
“It was previously shown that apigenin prevents LPS-induced atrogin-1 expression in C2C12 myotubes by regulating phosphorylation of JNK [24].”
From Apigenin Enhances Skeletal Muscle Hypertrophy and Myoblast Differentiation by Regulating Prmt7 (2017) · cites this paper as [24]
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- Authors
- SHIOTA, C., ABE, T., KAWAI, N., OHNO, A., TESHIMA-KONDO, S., MORI, H., TERAO, J., TANAKA, E., & NIKAWA, T.
- Affiliations
- Tokushima University (JP)
- ORCID
- Venue
- Journal of Nutritional Science and Vitaminology
- Published
- 2015
- Volume
- 61
- Issue
- 2
- Pages
- 188-194
- ISSN
- 0301-4800 (ISSN-L)
- 1881-7742
- OpenAlex
- W1884746705
- Cited by
- 46
- References
- 39
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Journal of Nutritional Science and Vitaminology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- flavonoids, atrogin-1/MAFbx, muscle atrophy, lipopolysaccharide, apigenin, luteolin, JNK signaling, skeletal muscle, C2C12 myotubes, atrogenes, inflammation, myotube diameter
- MeSH terms
- Animals, Cell Line, Inflammation, Phytotherapy, Muscle Proteins, Muscular Atrophy, Phosphorylation, Plant Extracts, Signal Transduction, Muscle, Skeletal, Muscle Fibers, Skeletal, MAP Kinase Signaling System, SKP Cullin F-Box Protein Ligases, Flavones, Apigenin, Luteolin, Mice
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