title: Astragalus polysaccharides decrease muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling in 5/6 nephrectomised rats.
abstract: BACKGROUND
  Existing evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research.
  
  
  OBJECTIVE
  In this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats.
  
  
  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.
authors.affiliation: Department of Traditional Chinese Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Nephrology, Southern Medical University TCM-Integrated Hospital, Guangzhou 510515, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Traditional Chinese Medicine, the First People's Hospital of Shunde Affiliated to Southern Medical University, Guangzhou 528300, China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Department of Traditional Chinese Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Nephrology, Southern Medical University TCM-Integrated Hospital, Guangzhou 510515, China.
authors.forename: De-Xiu
authors.initials: DX
authors.lastname: Chen
authors.affiliation: Department of Traditional Chinese Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Cong
authors.initials: YC
authors.lastname: Zou
authors.affiliation: Department of Endocrinology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Traditional Chinese Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Nephrology, Southern Medical University TCM-Integrated Hospital, Guangzhou 510515, China. Electronic address: weilianbo@163.com.
authors.forename: Lian-Bo
authors.initials: LB
authors.lastname: Wei
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001343:Autophagy / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects; D009392:Nephrectomy; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D025801:Ubiquitin; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex
keywords: Astragalus polysaccharides; Chronic kidney disease; Muscle wasting; Protein metabolism