Lu Lu1, Yan-Feng Huang2, De-Xiu Chen1, Ming Wang3, Yu-Cong Zou4, Heng Wan5, Lian-Bo Wei6. 1. 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. 2. Department of Traditional Chinese Medicine, the First People's Hospital of Shunde Affiliated to Southern Medical University, Guangzhou 528300, China. 3. Department of Traditional Chinese Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China. 4. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. 5. Department of Endocrinology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510280, China. 6. 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.
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.
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.