Standardized Curcuma xanthorrhiza Extract and Its Major Compound, Xanthorrhizol, Mitigate Cancer-Associated Muscle Atrophy in CT26-Bearing Mice by Inhibiting Catabolic Signaling Pathways

Cancer cachexia, defined by the gradual depletion of muscle and fat mass, is a complex multifactorial syndrome affecting up to 80% of cancer patients. This study investigated the effects of Curcuma xanthorrhiza extract (CXE) and xanthorrhizol (XAN) in ameliorating cancer-induced muscle atrophy in BALB/c mice. Treatment with CXE and XAN reversed muscle mass loss, grip strength decline, and decrease in myofiber size induced by cancer. In gastrocnemius muscle tissue, CXE and XAN downregulated the expression of nuclear factor kappa-beta (NF-κB), reducing the expression levels of proinflammatory cytokines. They also suppressed catabolic factors, including myostatin and ubiquitin-proteasome E3 ligases, and the nuclear translocation of forkhead box O3a. Furthermore, CXE and XAN promoted skeletal muscle anabolism by stimulating myogenesis and activating the phosphoinositide 3-kinase/protein kinase B signaling pathway. This activation subsequently upregulated the mammalian target of rapamycin and its downstream molecules. Overall, CXE and XAN effectively mitigated skeletal muscle catabolism induced by cancer cachexia and may serve as an intervention for inhibiting muscle atrophy in affected cancer patients if efficacy can be confirmed in human trials.