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

Ethnopharmacological relevanceExisting evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research.Aim of the studyIn this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats.Materials and methodsWe 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.ResultsData 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.ConclusionsOur results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.

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