Comprehensive characterisation of bioactive compounds in Boletus edulis as functional foods to improve muscle atrophy; through whole plant targeted metabolomics, network pharmacology, in vivo and in vitro experiments, molecular docking and molecular dynamics analysis

BE administered alone was able to slow down Lipopolysaccharide (LPS)-induced muscle atrophy. 996 non-volatile components were detected in BE by metabolomics, and GAPDH, TP53, AKT1, TNF-α and IL-6 were more strongly associated with muscle atrophy by using web-based pharmacological analyses. Folic acid, Cycloartenol and Sesamin active ingredients have greater potential to treat or alleviate muscle atrophy, molecular docking, molecular dynamics detected that Sesamin and AKT both have high binding energy, in vitro using C2C12 skeletal muscle cells to verify the efficacy of Sesamin and BE, found that in the presence of the LY294002 (PI3K inhibitor) and GSK21417 (AKT inhibitor) treatment conditions, the elimination of the up-regulation of the PI3K/AKT signaling pathway by Sesamin and BE and loss of biological efficacy. It suggests that BE may slow down or treat muscle atrophy through the PI3K/AKT signaling pathway, in which Sesamin plays a major role. Meanwhile BE and Sesamin were able to enhance the antioxidant level of C2C12 skeletal muscle cells.