Abstract
OBJECTIVE: To investigate the effects of Astragalus polysaccharide (APS) on skeletal muscle structure and function in D-galactose (D-gal)-induced C57BL/6J mice. METHODS: Eighteen male C57BL/6J mice of specific pathogen-free (SPF) grade, aged 8 weeks, were selected and divided into three groups: a control group (0.9% saline gavage for 16 weeks), a D-gal group (subcutaneous injection of 200 mg/kg D-galactose in the upper neck region, once daily for 8 weeks), and a D-gal + APS group (subcutaneous injection of 200 mg/kg D-galactose, once daily for 8 weeks, with concurrent administration of 100 mg/kg APS by gavage for 8 weeks). Body composition of the mice was assessed using the ImpediVET Laboratory Composition Measurement Analyzer. The pathological structure of the skeletal muscles was examined using hematoxylin and eosin (HE) staining, and the microstructure and mitochondrial alterations in skeletal muscle were observed under transmission electron microscopy. Protein expression levels of LC3II and PINK1 in skeletal muscle tissues were analyzed using Western blotting analysis. RESULTS: Compared to the control group, the D-gal-treated mice demonstrated substantial declines in grip strength, the cross-sectional area (CSA) of gastrocnemius muscle fibers, gastrocnemius weight, and the gastrocnemius weight-to-body weight ratio. APS administration markedly improved these parameters in the D-gal-treated mice. H&E staining showed muscle atrophy and senescence in the D-gal-treated mice, accompanied by deformed muscle cell morphology, which was mitigated by APS gavage. The D-gal-treated mice displayed swelling, cristae fracture, lysis, or complete loss, alongside reduced autophagy and increased lengths of bright bands, myofibrillar myonules, and H bands. However, administration of APS alleviated mitochondrial damage, promoted mitophagy, and reduced the lengths of these muscle tissue bands. Additionally, D-gal treatment significantly reduced LC3II and PINK1 protein expression in muscle tissues, while APS treatment notably elevated their expression levels. CONCLUSION: APS gavage ameliorates the structural and functional impairments in muscle tissues of the D-gal-treated mice by promoting mitochondrial autophagy.