Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38‐MAPK/FoxO3 pathway in cancer cachexia

Abstract Background Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone‐induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms. Methods C26 tumour‐bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF‐α‐induced C2C12 myotubes or ad‐mRFP‐GFP‐LC3B‐transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy‐lysosome system. The possible direct targets of CYA were searched using the biotin‐streptavidin pull‐down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay. Results The administration of CYA prevented body weight loss and muscle wasting in C26 tumour‐bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P