Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1
Abstract
The inflammatory cytokine tumor necrosis factor α (TNFα), upregulated in the obese condition, promotes protein degradation and is implicated in obesity-related skeletal muscle atrophy and age-related sarcopenia. Quercetin, a flavonoid, elicits antioxidative and anti-inflammatory activities. In this study, we investigated the effect of quercetin on TNFα-induced skeletal muscle atrophy as well as its potential mechanism of action. In this study, we observed that quercetin suppressed expression of TNFα-induced atrophic factors such as MAFbx/atrogin-1 and MuRF1 in myotubes, and it enhanced heme oxygenase-1 (HO-1) protein level accompanied by increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in myotubes. The HO-1 inhibitor ZnPP suppressed the inhibitory actions of quercetin on TNFα-induced atrophic responses and degradation of IκB-α in myotubes. Moreover, quercetin supplementation to high-fat diet-fed obese mice inhibited obesity-induced atrophic responses in skeletal muscle, accompanied by upregulation of HO-1 and inactivation of nuclear factor-kappa B (NF-κB), and the quercetin actions were attenuated in Nrf2-deficient mice. These findings suggest that quercetin protects against TNFα-induced muscle atrophy under obese conditions through Nrf2-mediated HO-1 induction accompanied by inactivation of NF-κB. Quercetin may be used as a dietary supplement to protect against obesity-induced skeletal muscle atrophy.
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Quercetin suppresses the expression of atrophic factors including MAFbx and MuRF1 induced by TNF-α injection under obese conditions in C57BL/6 mice.
“Kim et al. reported that quercetin suppresses the expression of atrophic factors including MAFbx and MuRF1 induced by TNF-α injection under obese conditions in C57BL/6 mice.”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [111]
Quercetin enhances heme oxygenase-1 protein level by the activation of nuclear translocation of Nrf2 and the inhibition of NF-κB in myotubes.
“Furthermore, quercetin enhances heme oxygenase-1 protein level by the activation of nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of NF-κB in myotubes [111].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [111]
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Lin, W., Zhao, Y., Liu, C., Yan, Y., & Ou, Q. (2022) · International Journal of Food Properties · doi:10.1080/10942912.2022.2127764 · Cited by 4 · see citing works
Pharmacological effects of denervated muscle atrophy due to metabolic imbalance in different periods
Qiu, J., CHANG, Y., LIANG, W., LIN, M., Xu, H., XU, W., ZHU, Q., ZHANG, H., & ZHANG, Z. (2023) · Biocell · doi:10.32604/biocell.2023.031043 · Cited by 3 · see citing works
The role of Heme oxygenase-1 (HO-1) in sepsis-associated organ damage: A systematic review
Li, T., Wang, D., Xu, Z., Xu, Z., Li, Z., Bai, X., Zhao, H., Yang, J., Liu, Y., & Wang, Y.-C. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156175 · Cited by 4 · see citing works
Natural compounds and programmed necrosis: pioneering a new frontier in cancer treatments
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Polyphenols as Therapeutic Approach to High Altitude Mediated Skeletal Muscle Impairments
Kushwaha, A. D., Bhardwaj, V., & Saraswat, D. (2021) · Defence Life Science Journal · doi:10.14429/dlsj.6.16344
Kim, S. O., Jeung, J.-S., Park, C., Lee, H., Choi, S. H., Kim, G., Kim, H. Y., Choi, Y. H., & Lee, E. H. (2022) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-021-0349-x
Research on Polyphenol Functions and Application on Products
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Preventing Muscle Atrophy by Polyphenols
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- Authors
- Kim, Y., Kim, C.-S., Joe, Y., Chung, H. T., Ha, T. Y., & Yu, R.
- Affiliations
- University of Ulsan (KR)
- Korea Food Research Institute (KR)
- Corresponding author
- Yu, Rina
- Venue
- Journal of Medicinal Food
- Publisher
- SAGE Publications
- Published
- 2018-06
- Volume
- 21
- Issue
- 6
- Pages
- 551-559
- ISSN
- 1096-620X (ISSN-L)
- 1557-7600
- OpenAlex
- W2791529386
- Cited by
- 69
- References
- 40
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 8 · 2022: 16 · 2021: 12 · 2020: 7 · 2019: 5 · 2018: 1
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Food (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Korea Food Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- quercetin, TNF-α, skeletal muscle atrophy, heme oxygenase-1, Nrf2, NF-κB, obesity, sarcopenia, myotubes, atrogin-1/MAFbx, MuRF1, protein degradation, high-fat diet, flavonoids
- MeSH terms
- Animals, Humans, Male, Mice, Inbred C57BL, Muscular Atrophy, Obesity, Quercetin, Tumor Necrosis Factor-alpha, Up-Regulation, Muscle Fibers, Skeletal, NF-E2-Related Factor 2, Mice, Heme Oxygenase-1
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