Abstract:
Objective In this study, we established a mouse model of cancer cachexia to explore the underlying mechanisms, and the skeletal muscle atrophy alleviating effects of elemene.
Methods 40 mice were randomly assigned into the following groups: a healthy group; a cachexia model group; a megestrol acetate?treated group; an elemene-treated group. Lewis lung cancer cells were injected subcutaneously to create a cancer cachexia model. After 14 days of elemene oral milk treatment, daily food intake, tumor weight, tumor-free weight, gastrocnemius and tibialis anterior muscle mass, and liver mass were measured, the cross-sectional area of the gastrocnemius muscle was detected by H&E staining, IL-6 and TNF-ɑ serum levels were evaluated by ELISA, and the expression of MAFBx and MURF-1 proteins in gastrocnemius muscle was monitored by Western blot.
Results Compared with those in the cachexia model group, the daily food intake, tumor-free weight, and gastrocnemius and tibialis anterior muscle mass were increased in the elemene group. The cross-sectional area of the gastrocnemius muscle was increased, serum IL-6 and TNF-ɑ levels were significantly decreased, and expression levels of MAFBx and MURF-1 proteins declined significantly (P < 0.05). Compared with that in the megestrol-acetate? treated group, the cross-sectional area of the gastrocnemius muscle was increased in the elemene-treated group, and serum IL-6 and TNF-ɑ levels and MAFBx and MURF-1 protein expression levels were reduced (P < 0.05).
Conclusions Elemene alleviates skeletal muscle atrophy in cancer cachexia, potentially by decreasing energy consumption, lowering serum TNF-α and IL-6 levels, attenuating MAFBx and MURF-1 protein expression in the skeletal muscle, and regulating the activity of the ubiquitin proteasome pathway (UPP) in mouse skeletal muscle.