Astragalus polysaccharide, a component of traditional Chinese medicine, inhibits muscle cell atrophy (cachexia) in an in vivo and in vitro rat model of chronic renal failure by activating the ubiquitin-proteasome pathway

Abstract

The present study aimed to determine the effect of Astragalus polysaccharide (APS) in an in vivo and in vitro rat model of muscle atrophy (cachexia) caused by chronic renal failure (CRF), along with the potential corresponding roles of atroglin-1 and the ubiquitin-proteasome pathway. A rat model of CRF was established using subtotal bilateral nephrectomy. It was observed by reverse transcription-quantitative polymerase chain reaction and western blot analysis that APS and the specific inhibitor of nuclear factor (NF)-κB, pyrrolidine dithiocarbamate (PDTC), significantly reduced the expression of atrogin-1, ubiquitin and the NF-κB subunit p65 mRNA in rat skeletal muscle in vivo and in vitro, respectively (P<0.05). NF-κB and PDTC also markedly reduced the expression of atrogin-1, ubiquitin and p65 protein. In addition, cultured rat myoblasts pretreated with tumor necrosis factor (TNF)-α exhibited significantly reduced expression of atrogin-1, ubiquitin and p65 mRNA in vitro (P<0.05). Fluorescence microscopy was subsequently used to evaluate TNF-α-treated myoblasts administered with APS or PDTC, whereby no evidence of muscle cell atrophy was observed in cells treated with APS. These data suggest that APS may delay muscle cell atrophy associated with cachexia in CRF by targeting atrogin-1 and the ubiquitin-proteasome pathway.

Modulating the metabolism by trimetazidine enhances myoblast differentiation and promotes myogenesis in cachectic tumor-bearing c26 mice

“…Additionally, a deeper analysis of the effects of TMZ during C2C12 differentition shows that the transcript levels of factors involved in myotube hypotrophy, namely atrogin-1/MAFbx and myostatin, decrease in TMZ-treated C2C12 myoblasts cultured in DM for 24h, to progressively return to control levels at 48h and 72h (Figure 4E ), while MuRF-1 mRNA levels are not affected by TMZ in the same conditions (Figure 4E ). We speculate that, since TMZ inhibits NF-kB [ 53 , 54 ] which is related to Atrogin expression, this might cause a reduction of Atrogin [ 55 ]. However, this point needs to be elucidated by additional studies.…”

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

“…CRF is considered as one of the most significant public health problems, with accumulating rates of occurrence and development [3]. There are about 10% of the general adult population affected by CRF worldwide, which is often complicated by sepsis and cardiovascular disease [4]. Previous study has revealed that CRF is characterized by slowly progressive chronic renal interstitial fibrosis (RIF) and accompanied with increased oxidative stress (OS) that is already found in the early stage of renal disease [5].…”

A Review of Complementary and Alternative Medicine Therapies on Muscular Atrophy: A Literature Review of In Vivo/In Vitro Studies

“…In addition, JPYS decoction not only inhibited FoxO3a activation and ubiquitin-proteasome system (UPS), but also increased Cox IV, NRF-1, and PGC-1 α [25]. Atrogin-1 and MuRF-1 were also measured in the study by Geng Z et al, and astragalus polysaccharide significantly reduced the expression of atrogin-1 and ubiquitin in rat skeletal muscle [38].…”