Cited by 67Adipose Tissue and MetabolismExercise and Physiological ResponsesMuscle Physiology and Disorders

Ursolic acid induces mitochondrial biogenesis through the activation of AMPK and PGC-1 in C2C12 myotubes: A possible mechanism underlying its beneficial effect on exercise endurance

Chen, Jihang, Wong, Hoi Shan, Leong, Pou Kuan, Leung, Hoi Yan, Chan, Wing Man, Ko, Kam Ming·2017·Food & Function

Abstract

Mitochondrial biogenesis, which involves an increase in mitochondrial number and the overall capacity of oxidative phosphorylation, is a critical determinant of skeletal muscle function. Recent findings have shown that some natural products can enhance mitochondrial adaptation to aerobic exercise, which in turn improves exercise performance, presumably by delaying muscle fatigue. Ursolic acid (UA), a natural triterpene, is commonly found in various vegetables and fruits. In the current study, UA was shown to increase mitochondrial mass and ATP generation capacity, with a concomitant production of a low level of mitochondrial reactive oxygen species (ROS) in C2C12 myotubes. Mitochondrial ROS, in turn, activated the redox sensitive adenosine monophosphate-dependent protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1(PGC-1) pathway. The activation of AMPK/PGC-1 further increased the expression of cytochrome c oxidase (COX) and uncoupling protein 3. Animal studies showed that UA can also dose-dependently increase the endurance exercise capacity in mice, as assessed by a weight-loaded swimming test and a hanging wire test. Our findings suggest that UA may induce mitochondrial biogenesis through the activation of AMPK and PGC-1 pathways in skeletal muscle, thereby offering a promising prospect for its use to enhance exercise endurance and alleviating fatigue in humans.

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Crossref · 10.1039/c7fo00127d

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Authors
Chen, J., Wong, H. S., Leong, P. K., Leung, H. Y., Chan, W. M., & Ko, K. M.
Affiliations
  • Hong Kong University of Science and Technology (HK)
  • Buck Institute for Research on Aging (US)
Corresponding author
Ko, Kam Ming
Venue
Food & Function
Published
2017
Volume
8
Issue
7
Pages
2425-2436
ISSN
  • 2042-6496 (ISSN-L)
  • 2042-650X
OpenAlex
W2626882131
Cited by
67
References
41
Citations by year
2026: 7 · 2025: 10 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 6
FWCI
4.05
Type
journal article
Language
en
Open access
closed
Locations
  • Food & Function (publishedVersion)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
National Natural Science Foundation of China (81603356)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
ursolic acid, mitochondrial biogenesis, AMPK, PGC-1, C2C12 myotubes, skeletal muscle, exercise endurance, mitochondrial reactive oxygen species, cytochrome c oxidase, UCP3, muscle fatigue, triterpenoids, oxidative phosphorylation
MeSH terms
Ursolic Acid, Adenosine Monophosphate, Animals, Fatigue, Humans, Male, Mice, Inbred ICR, Mitochondria, Oxidation-Reduction, Phosphorylation, Physical Endurance, Transcription Factors, Triterpenes, Reactive Oxygen Species, Muscle, Skeletal, Muscle Fibers, Skeletal, Mice, AMP-Activated Protein Kinases

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