Cinnamaldehyde regulates H2O2‐induced skeletal muscle atrophy by ameliorating the proteolytic and antioxidant defense systems
Abstract
Abstract Skeletal muscle atrophy/wasting is associated with impaired protein metabolism in diverse physiological and pathophysiological conditions. Elevated levels of reactive oxygen species (ROS), disturbed redox status, and weakened antioxidant defense system are the major contributing factors toward atrophy. Regulation of protein metabolism by controlling ROS levels and its associated catabolic pathways may help in treating atrophy and related clinical conditions. Although cinnamaldehyde (CNA) enjoys the established status of antioxidant and its role in ROS management is reported, impact of CNA on skeletal muscle atrophy and related pathways is still unexplored. In the current study, the impact of CNA on C2C12 myotubes and the possible protection of cultured cells from H 2O 2‐induced atrophy is examined. Myotubes were treated with H 2O 2 in the presence and absence of CNA and the changes in the antioxidative, proteolytic systems, and mitochondrial functions were scored. Morphological analysis showed significant protective effects of CNA on length, diameter, and nuclei fusion index of myotubes. The evaluation of biochemical markers of atrophy; creatine kinase, lactate dehydrogenase, succinate dehydrogenase along with the study of muscle‐specific structural protein (i.e., myosin heavy chain‐fast [MHCf] type) showed significant protection of proteins by CNA. CNA pretreatment not only checked the activation of proteolytic systems (ubiquitin‐proteasome E3‐ligases [MuRF1/Atrogin1]), autophagy [Beclin1/LC3B], cathepsin L, calpain, caspase), but also prevented any alteration in the activities of antioxidative defense enzymes (catalase, glutathione‐ S‐transferase, glutathione‐peroxidase, superoxide dismutase, glutathione reductase). The results suggest that CNA protects myotubes from H 2O 2‐induced atrophy by inhibiting/resisting the amendments in proteolytic systems and maintains cellular redox‐balance.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cinnamaldehyde protects H2O2-induced C2C12 myotubes atrophy by inhibiting the expression of MuRF1 and MAFbx and maintaining the balance of cellular redox.
“Cinnamaldehyde protects H2O2-induced C2C12 myotubes atrophy by inhibiting the expression of MuRF1 and MAFbx and maintaining the balance of cellular redox [155].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [155]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction
Ohkawa, H., Ohishi, N., & Yagi, K. (1979) · Analytical Biochemistry · doi:10.1016/0003-2697(79)90738-3 · Cited by 29,460 · see citing works
Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42083-8 · Cited by 18,394 · see citing works
A SPECTROPHOTOMETRIC METHOD FOR MEASURING THE BREAKDOWN OF HYDROGEN PEROXIDE BY CATALASE
Beers, R. F., & Sizer, I. W. (1952) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50881-x · Cited by 6,781 · see citing works
MORON, M., DePierre, J. W., & Mannervik, B. (1979) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(79)90289-7 · Cited by 4,214 · see citing works
A modified spectrophotometric assay of superoxide dismutase.
Kakkar, P., Das, B., & Viswanathan, P. N. (1984) · PubMed · Cited by 3,553 · see citing works
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953 · see citing works
Glutathione, oxidative stress and neurodegeneration
Schulz, J. B., Lindenau, J. H., Seyfried, J., & DICHGANS, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01595.x · Cited by 1,215 · see citing works
Antioxidant and free radical scavenging activity of Spondias pinnata
Hazra, B., Biswas, S., & Mandal, N. (2008) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-8-63 · Cited by 640 · see citing works
Cancer cachexia is regulated by selective targeting of skeletal muscle gene products
Acharyya, S., Ladner, K. J., Nelsen, L., Damrauer, J. S., Reiser, P. J., Swoap, S. J., & D, D. C. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20174 · Cited by 541 · see citing works
Reactive Oxygen Species: Impact on Skeletal Muscle
Powers, S. K., Ji, L. L., Kavazis, A. N., & Jackson, M. J. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100054 · Cited by 509 · see citing works
Sandri, M. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.056 · Cited by 451 · see citing works
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
Oxidative Stress, Chronic Disease, and Muscle Wasting
Moylan, J. S., & Reid, M. B. (2007) · Muscle & Nerve · doi:10.1002/mus.20743 · Cited by 416 · see citing works
Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety
Zhu, R., Liu, H., Liu, C., Wang, L., Ma, R., Chen, B., Li, L., Niu, J., Fu, M., Zhang, D., et al. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.05.019 · Cited by 310 · see citing works
Megestrol acetate for treatment of anorexia-cachexia syndrome
García, V. R., Briz, E. L., Sanchís, R. C., Perales, J. L. G., & Bort-Martí, S. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004310.pub3 · Cited by 296 · see citing works
Age-related changes in glutathione and glutathione-related enzymes in rat brain
Zhu, Y., Carvey, P. M., & Ling, Z. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.063 · Cited by 279 · see citing works
The TWEAK–Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice
Mittal, A., Bhatnagar, S., Kumar, A., Lach-Trifilieff, E., Wauters, S., Li, H., Makonchuk, D. Y., Glass, D. J., & Kumar, A. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200909117 · Cited by 250 · see citing works
Self-citationWeight Loss as a Predictor of Survival and Disease Progression in HIV Infection
Wheeler, D. A., Gibert, C. L., Launer, C. A., Muurahainen, N., Elion, R., Abrams, D. I., & Bartsch, G. E. (1998) · Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology · doi:10.1097/00042560-199805010-00012 · Cited by 230 · see citing works
Kavazis, A. N., Talbert, E. E., Smuder, A. J., Hudson, M. B., Nelson, W. B., & Powers, S. K. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.01.002 · Cited by 205 · see citing works
Metabolic Consequences of Muscle Disuse Atrophy
Stein, T. P., & Wade, C. E. (2005) · Journal of Nutrition · doi:10.1093/jn/135.7.1824s · Cited by 195 · see citing works
Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-κB
Sriram, S., Subramanian, S., Sathiakumar, D., Venkatesh, R., Salerno, M. S., McFarlane, C. D., Kambadur, R., & Sharma, M. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00734.x · Cited by 189 · see citing works
Camacho, S., Michlig, S., de Senarclens-Bezençon, C., Meylan, J., Meystre, J., Pezzoli, M., Markram, H., & le Coutre, J. (2015) · Scientific Reports · doi:10.1038/srep07919 · Cited by 189 · see citing works
Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action
Dutt, V., Gupta, S. K., Dabur, R., Injeti, E. R., & Mittal, A. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.05.010 · Cited by 174 · see citing works
Self-citationOxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm
Whidden, M. A., Smuder, A. J., Wu, M. H., Hudson, M. B., Nelson, W. B., & Powers, S. K. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00098.2010 · Cited by 160 · see citing works
Ten misconceptions about antioxidants
Bast, A., & Haenen, G. R. M. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.05.010 · Cited by 157 · see citing works
Calpain-1 is required for hydrogen peroxide-induced myotube atrophy
McClung, J. M., Judge, A. R., Talbert, E. E., & Powers, S. K. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00497.2008 · Cited by 126 · see citing works
Zhao, H., Zhang, M., Zhou, F., Cao, W., Bi, L., Xie, Y., Yang, Q., & Wang, S. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.10.017 · Cited by 124 · see citing works
Lipoamide Dehydrogenase, Glutathione Reductase, Thioredoxin Reductase, and Thioredoxin
Williams, C. H., Zanetti, G., Arscott, L. D., et al. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99415-9 · Cited by 120 · see citing works
George, R. C., Lew, J., & Graves, D. J. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122113 · Cited by 112 · see citing works
A simplified immunohistochemical classification of skeletal muscle fibres in mouse
Kammoun, M., Cassar‐Malek, I., Meunier, B., & Picard, B. B. (2014) · European Journal of Histochemistry · doi:10.4081/ejh.2014.2254 · Cited by 108 · see citing works
Can Antioxidants Protect Against Disuse Muscle Atrophy?
Powers, S. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0255-x · Cited by 101 · see citing works
Mizunoya, W., Wakamatsu, J., Tatsumi, R., & Ikeuchi, Y. (2008) · Analytical Biochemistry · doi:10.1016/j.ab.2008.02.021 · Cited by 100 · see citing works
Subash‐Babu, P., Alshatwi, A. A., & Savarimuthu Ignacimuthu, S. J. (2014) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2013.100 · Cited by 96 · see citing works
Shi, S. Y., Lu, S.-Y., Sivasubramaniyam, T., Revelo, X. S., Cai, E. P., Luk, C. T., Schroer, S. A., Patel, P., Kim, R. H., Bombardier, É., et al. (2015) · Nature Communications · doi:10.1038/ncomms8415 · Cited by 85 · see citing works
The Molecular Mechanisms of Calpains Action on Skeletal Muscle Atrophy
HUANG, J., & Zhu, X. (2016) · Physiological Research · doi:10.33549/physiolres.933087 · Cited by 84 · see citing works
Lv, C., Xing, Y., Zeng, H., Liu, R., & Zhang, W. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.09.009 · Cited by 83 · see citing works
Muscle immobilization activates mitophagy and disrupts mitochondrial dynamics in mice
Kang, C., Yeo, D., & Ji, L. L. (2016) · Acta Physiologica · doi:10.1111/apha.12690 · Cited by 79 · see citing works
Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscle cells
Kumar, N., & Dey, C. S. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01509-5 · Cited by 75 · see citing works
Huang, S., Taylor, N. L., Ströher, E., Fenske, R., & Millar, A. H. (2012) · The Plant Journal · doi:10.1111/tpj.12041 · Cited by 75 · see citing works
Toxicokinetics of cinnamaldehyde in F344 rats
Yuan, J. H., Dieter, M. P., Bucher, J. R., et al. (1992) · Food and Chemical Toxicology · doi:10.1016/0278-6915(92)90109-x · Cited by 75 · see citing works
A rapid β-NADH-linked fluorescence assay for lactate dehydrogenase in cellular death
Moran, J. H., & Schnellmann, R. G. (1996) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/1056-8719(96)00071-8 · Cited by 72 · see citing works
Acetylation and deacetylation—novel factors in muscle wasting
Alamdari, N., Aversa, Z., Castillero, E., & Hasselgren, P.-O. J. (2012) · Metabolism · doi:10.1016/j.metabol.2012.03.019 · Cited by 71 · see citing works
Nuclear factor-κB signaling contributes to mechanical ventilation-induced diaphragm weakness*
Smuder, A. J., Hudson, M. B., Nelson, W. B., Kavazis, A. N., & Powers, S. K. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182374a84 · Cited by 63 · see citing works
Reactive Oxygen Species: Impact on Skeletal Muscle
Powers, S. K., Ji, L. L., Kavazis, A. N., & Jackson, M. J. (2011) · Comprehensive physiology · doi:10.1002/j.2040-4603.2011.tb00348.x · Cited by 63 · see citing works
The Preventive Effect of β-Carotene on Denervation-Induced Soleus Muscle Atrophy in Mice
Ogawa, M., Kariya, Y., Kitakaze, T., Yamaji, R., Harada, N., Sakamoto, T., Hosotani, K., Nakano, Y., & Inui, H. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114512003297 · Cited by 58 · see citing works
Dawidowicz, A. L., & Olszowy‐Tomczyk, M. (2011) · European Food Research and Technology · doi:10.1007/s00217-011-1451-7 · Cited by 54 · see citing works
Nikzamir, A., Palangi, A., Kheirollaha, A., Tabar, H., Malakaskar, A., Shahbazian, H. B., & Fathi, M. (2014) · Iranian Red Crescent Medical Journal · doi:10.5812/ircmj.13426 · Cited by 53 · see citing works
Farag, M. R., Alagawany, M. M., & Tufarelli, V. (2016) · Drug and Chemical Toxicology · doi:10.1080/01480545.2016.1193866 · Cited by 52 · see citing works
Protective effect of myokine IL-15 against H2O2-mediated oxidative stress in skeletal muscle cells
Li, F., Li, Y., Tang, Y., Lin, B., Kong, X., Oladele, O. A., & Yin, Y. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3665-9 · Cited by 48 · see citing works
Yang, D., Liang, X., Shi, Y., Sun, Q. Y., Liu, D., Liu, W., & Zhang, H. (2015) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-015-2103-8 · Cited by 44 · see citing works
A selective colorimetric assay for cathepsin L using Z-Phe-Arg-4-methoxy-β-naphthylamide
Kamboj, R. C., Pal, S., Raghav, N., et al. (1993) · Biochimie · doi:10.1016/0300-9084(93)90042-q · Cited by 43 · see citing works
Wang, L., Wang, Z., Yang, K., Shu, G., Wang, S., Gao, P., Zhu, X., Xi, Q., Zhang, Y., & Jiang, Q. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b02193 · Cited by 39 · see citing works
Supinski, G. S., Ji, X., & Callahan, L. A. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90849.2008 · Cited by 36 · see citing works
Prathapan, A., Nampoothiri, S. V., Mini, S., & Raghu, K. G. (2012) · PubMed · Cited by 29 · see citing works
Xu, F., Wang, F., Wen, T., Sang, W., Wang, D., & Zeng, N. (2017) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2017.1355377 · Cited by 27 · see citing works
Bodakhe, S. H., Singh, A., Khan, S. A., & Choudhary, R. (2016) · Journal of pharmacopuncture · doi:10.3831/kpi.2016.19.015 · Cited by 21 · see citing works
Furutani, Y., Murakami, M., & Funaba, M. (2009) · Cell Biochemistry and Function · doi:10.1002/cbf.1614 · Cited by 18 · see citing works
Understanding cancer-induced cachexia
Penet, M., Winnard, P. T., Jacobs, M. A., et al. (2011) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e32834c49ba · Cited by 15 · see citing works
Sivakumar, A. S., & Hwang, I. (2015) · Journal of Biosciences · doi:10.1007/s12038-015-9503-y · Cited by 13 · see citing works
Efficient and modified protocol for zymography to detect muscle specific calpain activity
Dutt, V., Kaur, N., Gupta, P., et al. (2017) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2017.02.011 · Cited by 11 · see citing works
Self-citationMagnesium deficiency up‐regulates Myod expression in rat skeletal muscle and C2C12 myogenic cells
Furutani, Y., Funaba, M., & Matsui, T. (2011) · Cell Biochemistry and Function · doi:10.1002/cbf.1790 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy
Wang, Y., Liu, Q., Quan, H., Kang, S.-G., Huang, K., & Tong, T. (2021) · Nutrients · doi:10.3390/nu13061914 · Cited by 61 · see citing works
S-Allyl Cysteine: A Potential Compound against Skeletal Muscle Atrophy
Gupta, P., Dutt, V., Kaur, N., Kalra, P., Gupta, S., Dua, A., Dabur, R., Saini, V., & Mittal, A. (2020) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2020.129676 · Cited by 25 · see citing works
Self-citation
- Authors
- Kaur, N., Gupta, P., Saini, V., Sherawat, S., Gupta, S., Dua, A., Kumar, V., Injeti, E., & Mittal, A.
- Affiliations
- Kurukshetra University (IN)
- All India Institute of Medical Sciences (IN)
- Maharishi Markandeshwar University, Mullana (IN)
- Cedarville University (US)
- Corresponding author
- Mittal, Ashwani
- ORCID
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2018-10-14
- Volume
- 234
- Issue
- 5
- Pages
- 6194-6208
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2896259626
- Cited by
- 40
- References
- 62
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 9 · 2019: 4
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research (IRIS Cell No. 2012‐2656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- cinnamaldehyde, skeletal muscle atrophy, hydrogen peroxide, reactive oxygen species, oxidative stress, proteolytic system, ubiquitin-proteasome system, autophagy, antioxidant defense, myotubes, redox homeostasis, myosin heavy chain, MuRF1, atrogin-1, calpain, cathepsin L, mitochondrial function
- MeSH terms
- Acrolein, Animals, Antioxidants, Cell Line, Hydrogen Peroxide, Muscular Atrophy, Muscle, Skeletal, Mice, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review