Astragalus Polysaccharide Suppresses Skeletal Muscle Myostatin Expression in Diabetes: Involvement of ROS-ERK and NF-κB Pathways

Abstract

Objective. The antidiabetes drug astragalus polysaccharide (APS) is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS. Methods. APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells. Results. APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK), and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively. Conclusion. Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.

Effect of Astragalus polysaccharides on ovariectomy-induced osteoporosis in mice

“…Astragalus polysaccharide (APS) is one of the active ingredients of Radix Astragali. It has been shown to exert various pharmacological activities, including antiinflammatory (Luo et al, 2015;Wei et al, 2016), antioxidant (Li et al, 2010;Yan et al, 2010), anti-diabetic (Liu et al, 2013), and anti-tumor activity (Yang et al, 2013). Furthermore, APS treatment ameliorated adjuvant-induced arthritis in rats in a dose-dependent manner (Jiang et al, 2010).…”

AstragalusPolysaccharide Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the PI3k/Akt and p38MAPK Pathways

“…Astragalus species derivatives are crude drugs that have been widely used in traditional Chinese medicine for thousands of years as antiperspirant, antihypertensive, diuretic, and tonic treatments [8]. Studies from our group and others have indicated that Astragalus polysaccharide (APS), the extract from Astragalus membranaceus , exerts strong antitumor and antiglomerulonephritis activity [9] and effectively alleviates inflammation-induced artery endothelium cell injury and atherosclerosis [7].…”

Purification, characterization, and biological activities of purified polysaccharides extracted from the gray oyster mushroom [Pleurotus sajor-caju (Fr.) Sing.]

“…Some insight about the effects of polysaccharides on the whole organism and muscle cells came from many studies that utilized Astragalus polysaccharides (APS) extracted from Astragalus membranaceus Bunge. For example, it was shown that APS lowered blood glucose in diabetic rats by increasing the overall phosphorylation of AMP‐activated protein kinase alpha subunit (AMPKα) and expression of glucose transporter 4 (GLUT‐4) gene in skeletal muscles (M. Liu et al, ; Zou, Mao, Wang, Liu, & Ou‐Yang, ). In C2C12 mouse myotubes, APS ameliorated palmitate induced insulin resistance through the inhibition of NF‐κB activation and inhibition of extracellular signal‐regulated kinase (ERK) (M. Liu et al, ; Zhao, Zhang, Ding, Wang, & Li, ).…”

“…For example, it was shown that APS lowered blood glucose in diabetic rats by increasing the overall phosphorylation of AMP‐activated protein kinase alpha subunit (AMPKα) and expression of glucose transporter 4 (GLUT‐4) gene in skeletal muscles (M. Liu et al, ; Zou, Mao, Wang, Liu, & Ou‐Yang, ). In C2C12 mouse myotubes, APS ameliorated palmitate induced insulin resistance through the inhibition of NF‐κB activation and inhibition of extracellular signal‐regulated kinase (ERK) (M. Liu et al, ; Zhao, Zhang, Ding, Wang, & Li, ). Likewise, a previous study revealed that APS stimulated the L6 muscle cells in dose‐ and time‐dependent manner (J. Liu et al, ).…”