Astragalus Polysaccharide Alleviates COPD-Associated Skeletal Muscle Dysfunction Through Suppression of Inflammation and Cellular Senescence

Abstract

Astragalus polysaccharide (APS) exhibits various pharmacological properties. However, scientific evidence to support its usage in chronic obstructive pulmonary disease (COPD)-associated skeletal muscle dysfunction is limited. This study aimed to investigate the effects of APS and its underlying mechanisms in cigarette smoke (CS)-induced COPD-associated skeletal muscle dysfunction in mice and CS extract (CSE)-induced atrophy in C2C12 myotubes. In vivo, APS significantly attenuated CS-induced weight loss, pulmonary inflammation, and lung structural damage. APS ameliorated skeletal muscle atrophy, evidenced by restored muscle weight, reduced fibrosis, and improved histoarchitecture. This was accompanied by the downregulation of atrophy markers (Atrogin-1and MuRF-1), pro-inflammatory cytokines (IL-6, TNF-α, CXCL1, CCL2, CXCL2 and GM-CSF), and senescence markers (p16, p21and p53) in skeletal muscle. In vitro, APS protected C2C12 myotubes from CSE-induced wasting, preventing reductions in myotube diameter and myogenic factor expression (MyoD, and Myogenin), while suppressing the upregulation of Atrogin-1, MuRF-1, IL-6, TNF-α, β-galactosidase activity and p53). Our findings demonstrated that APS effectively alleviated COPD-associated skeletal muscle dysfunction in both animal and cellular models. This protective effect is mediated through the concurrent suppression of inflammatory cascades and cellular senescence via NF-κB/p53 signaling pathway. This study provides preclinical evidence supporting APS as a promising functional food or supplement to mitigate COPD-associated skeletal muscle dysfunction.