{"title":"3-(4-Hydroxy-3-methoxyphenyl) propionic acid mitigates dexamethasone-induced muscle atrophy by attenuating Atrogin-1 and MuRF-1 expression in mouse C2C12 skeletal myotubes.","authors":"Anayt Ulla, Md Mizanur Rahman, Takayuki Uchida, Hiroyuki Kayaki, Yosuke Nishitani, Susumu Yoshino, Hiroshige Kuwahara, Takeshi Nikawa","doi":"10.3164/jcbn.23-70","DOIUrl":null,"url":null,"abstract":"<p><p>3-(4-Hydroxy-3-methoxyphenyl) propionic acid is an <i>in vivo</i> metabolite of 4-hydroxy-3-methoxycinnamic acid which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid on muscle atrophy induced by dexamethasone was investigated using mouse C2C12 skeletal myotubes. Dexamethasone treatment (10 μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1, along with their upstream regulator Krüppel-like factor 15. Dexamethasone dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 μM 3-(4-hydroxy-3-methoxyphenyl) propionic acid treatment significantly attenuated dexamethasone-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. 3-(4-Hydroxy-3-methoxyphenyl) propionic acid also prevented dexamethasone-induced Krüppel-like factor 15 and FoxO3a expression. In conclusion, these results suggest that <i>in vivo</i> metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as 3-(4-hydroxy-3-methoxyphenyl) propionic acid ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"76 1","pages":"16-24"},"PeriodicalIF":2.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782781/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Biochemistry and Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3164/jcbn.23-70","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
3-(4-Hydroxy-3-methoxyphenyl) propionic acid is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid on muscle atrophy induced by dexamethasone was investigated using mouse C2C12 skeletal myotubes. Dexamethasone treatment (10 μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1, along with their upstream regulator Krüppel-like factor 15. Dexamethasone dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 μM 3-(4-hydroxy-3-methoxyphenyl) propionic acid treatment significantly attenuated dexamethasone-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. 3-(4-Hydroxy-3-methoxyphenyl) propionic acid also prevented dexamethasone-induced Krüppel-like factor 15 and FoxO3a expression. In conclusion, these results suggest that in vivo metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as 3-(4-hydroxy-3-methoxyphenyl) propionic acid ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.
期刊介绍:
Journal of Clinical Biochemistry and Nutrition (JCBN) is
an international, interdisciplinary publication encompassing
chemical, biochemical, physiological, pathological, toxicological and medical approaches to research on lipid peroxidation, free radicals, oxidative stress and nutrition. The
Journal welcomes original contributions dealing with all
aspects of clinical biochemistry and clinical nutrition
including both in vitro and in vivo studies.