2. Academic Validation
  3. γ-Tocotrienol attenuates oxidative stress and preserves mitochondrial function in inflammation-induced muscle atrophy

γ-Tocotrienol attenuates oxidative stress and preserves mitochondrial function in inflammation-induced muscle atrophy

  • Redox Biol. 2025 Sep 19:87:103874. doi: 10.1016/j.redox.2025.103874.
Jun Yi Chong 1,  Tsui-Chin Huang 2,  Sheng-Ming Chueh 3,  Cheng-Yi Ma 3,  Tzu-Ting Kuo 4,  Jia-Jun He 5,  Yii-Jwu Lo 6,  Kuan-Chieh Peng 7,  Mohamed Ali 8,  Hsin-Yi Chang 9,  Shih-Min Hsia 10
Affiliations

Affiliations

  • 1 School of Nutrition and Health Sciences, Taipei Medical University, Taipei, 110301, Taiwan.
  • 2 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, 110301, Taiwan; PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 110301, Taiwan.
  • 3 Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, 110301, Taiwan; Graduate Institute of Life Sciences, National Defense Medical University, Taipei, 114201, Taiwan.
  • 4 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, 110301, Taiwan; Department of Research and Development, National Defense Medical University, Taipei, 114201, Taiwan.
  • 5 Graduate Institute of Medical Sciences, National Defense Medical University, Taipei, 114201, Taiwan.
  • 6 PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 110301, Taiwan.
  • 7 Graduate Institute of Life Sciences, National Defense Medical University, Taipei, 114201, Taiwan.
  • 8 Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, 60637, USA.
  • 9 Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, 110301, Taiwan; Graduate Institute of Life Sciences, National Defense Medical University, Taipei, 114201, Taiwan; Department of Research and Development, National Defense Medical University, Taipei, 114201, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical University, Taipei, 114201, Taiwan. Electronic address: hsinyi.chang@mail.ndmctsgh.edu.tw.
  • 10 School of Nutrition and Health Sciences, Taipei Medical University, Taipei, 110301, Taiwan; Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, 110301, Taiwan; School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, 110301, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, 110301, Taiwan; TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, 110301, Taiwan. Electronic address: bryanhsia@tmu.edu.tw.
PMID: 41005207 DOI: 10.1016/j.redox.2025.103874
Abstract

Muscle atrophy, marked by the loss of skeletal muscle mass and strength, presents a major health concern with diverse etiologies, including chronic inflammation. Effective interventions are urgently needed for its prevention and treatment. Although α-tocopherol, the most abundant form of vitamin E, is known for its antioxidant benefits in muscle health, γ-tocotrienol exhibits superior antioxidant and anti-inflammatory properties. This study investigates the protective effects of γ-tocotrienol against muscle atrophy and compares its efficacy with α-tocopherol. Muscle atrophy was induced in differentiated C2C12 myotubes using lipopolysaccharide (LPS), with vitamin E pre-treatment applied prior to LPS challenge. Myotube morphology, expression of atrophy-related markers, and underlying molecular pathways were examined through immunofluorescence, western blotting, and quantitative proteomics. LPS treatment induced significant myotube atrophy without affecting cell viability. Notably, γ-tocotrienol pre-treatment preserved myotube size and suppressed key atrophy markers, including the E3 ubiquitin ligases MuRF-1 and Fbxo32/Atrogin-1. Proteomic analysis quantified 5,371 proteins and revealed that γ-tocotrienol alleviated atrophy by enhancing extracellular matrix organization and attenuating oxidative stress and mitochondrial dysfunction. These protective effects were further confirmed in vivo, where γ-tocotrienol administration preserved muscle strength, suppressed pro-inflammatory signaling, and restored mitochondrial biogenesis in LPS-treated mice. Collectively, these findings demonstrate that γ-tocotrienol offers superior protection against muscle atrophy compared to α-tocopherol, highlighting its therapeutic potential for individuals at risk of muscle wasting.

Keywords

Mitochondrial oxidative stress; Muscle atrophy; Proteomics; Vitamin E; γ-Tocotrienol.

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