Effects of Ginsenoside Rg3 on fatigue resistance and SIRT1 in aged rats

Toxicology. 2018 Nov 1:409:144-151. doi: 10.1016/j.tox.2018.08.010. Epub 2018 Aug 23.


Background: Ginsenoside Rg3 (Rg3) is one of the key components of a frequently used herbal tonic panax ginseng for fatigue treatment. However, the molecular mechanisms of Rg3 on anti-fatigue effects have not been completely understood yet.

Methods and materials: We built a postoperative fatigue syndrome (POFS) model and tried to elucidate the molecular mechanisms responsible for anti-fatigue effects of Rg3. 160 aged male rats were randomly divided into four groups (n = 40/group): normal group, Rg3-treated normal group (Rg3 group), postoperative fatigue syndrome model group (POFS group) and Rg3-treated postoperative fatigue syndrome model group (POFS + Rg3 group). The open field test (OFT) was used to assess general activity and exploratory behavior of rats in different groups. We then analyzed total cholesterol (TC), serum triglyceride (TG) and lactate dehydrogenase (LDH) in the blood, as well as superoxide dismutase (SOD), malondialdehyde (MDA), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in skeletal muscles of rats. We also detected the influence of Rg3 on silent information regulator of transcription 1 (sirtuin1, SIRT1) activity and protein 53 (p53) transcriptional activity in vitro.

Results: Rg3 significantly increased the journey distance and rearing frequency, while slowed down the rest time. The serum concentrations of TC, TG and LDH were all up-regulated by Rg3. Meanwhile, Rg3 increased concentrations of SOD, but also decreased MDA release out of skeletal muscles. The mRNA expressions of PGC-1α and PEPCK were also enhanced by Rg3. Besides, Rg3 could activate SIRT1 and suppress p53 transcriptional activity in the biological process.

Discussion and conclusion: Rg3 could improve exercise performance and resist fatigue possibly through elevating SIRT1 deacetylase activity.

Keywords: Fatigue; Ginsenoside Rg3; Silent information regulator of transcription 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Behavior, Animal / drug effects
  • Fatigue / metabolism
  • Fatigue / physiopathology
  • Fatigue / prevention & control*
  • Ginsenosides / pharmacology*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Malondialdehyde / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Rats, Sprague-Dawley
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Superoxide Dismutase / metabolism
  • Tumor Suppressor Protein p53 / genetics


  • Ginsenosides
  • Intracellular Signaling Peptides and Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Tumor Suppressor Protein p53
  • ginsenoside Rg3
  • Malondialdehyde
  • Superoxide Dismutase
  • Sirt1 protein, rat
  • Sirtuin 1
  • Pck1 protein, rat
  • Phosphoenolpyruvate Carboxykinase (GTP)