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

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 SpragueDawley 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-alpha, 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 0.2 mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2 mg/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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.