Integrated transcriptomics and metabolomics studies reveal the therapeutic effects of Astragalus polysaccharides on cancer cachexia muscle atrophy.

Cancer cachexia (CC) is a condition causing significant muscle loss in advanced cancer patients, severely impacting their quality of life and life expectancy. The autophagy-lysosome system is a key pathway in muscle depletion in CC, but targeted therapies are lacking. This study investigates how Astragalus polysaccharides (APS) from the traditional Chinese herb Astragalus membranaceus alleviate muscle wasting in CC mice. Mice were divided into control, model, and APS high-dose groups. Results show high-dose APS significantly improved grip strength and muscle fiber cross-sectional area in CC mice. Transcriptomic analysis revealed differentially expressed genes (DEGs) enriched in autophagy and mitochondrial autophagy pathways. Electron microscopy showed APS reduced autophagic vesicles and protected muscle and mitochondria. Metabolomic analysis indicated APS regulates the expression of nitric oxide synthase (NOS). APS protects against muscle wasting in CC by suppressing excessive autophagy and reducing the expression of NOS, suggesting it as a potential therapeutic agent for mitigating muscle depletion in cancer cachexia.