Astragalus polysaccharides decrease muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling in 5/6 nephrectomised rats

J Ethnopharmacol. 2016 Jun 20:186:125-135. doi: 10.1016/j.jep.2016.03.068. Epub 2016 Apr 2.

Abstract

Ethnopharmacological relevance: Existing evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research.

Aim of the study: In this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats.

Materials and methods: We performed 5/6 nephrectomy or sham operation in 160 6-week-old Sprague-Dawley rats, and feed animals with or without 2% APS for 155 days. After treatment, we compared the change of weight, muscle fibre, protein metabolism, pro-inflammatory factors (TNF-α, IL-15, CRP) and oxidative factors (MDA, SOD) among each group. In addition, we detected the Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo and in vitro.

Results: Data in vivo show 2% APS could alleviate weight loss and improve protein metabolism in nephrectomised rats. The levels of serum pro-inflammatory factors and oxidative factors were restored by APS treatment. In molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose of APS is 0.2mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2mg/mL APS on atrophy and autophagy.

Conclusions: Our results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.

Keywords: Astragalus polysaccharides; Chronic kidney disease; Muscle wasting; Protein metabolism.

MeSH terms

  • Animals
  • Astragalus Plant / chemistry*
  • Autophagy / physiology
  • Cell Line
  • Gene Expression Regulation / drug effects
  • Gene Silencing
  • Male
  • Muscle, Skeletal / pathology
  • Myoblasts / drug effects
  • Nephrectomy*
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism*

Substances

  • Polysaccharides
  • Ubiquitin
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Proteasome Endopeptidase Complex