Skeletal muscle
atrophy, the most characteristic feature of
cancer cachexia, often occurs in patients with
cancer undergoing
chemotherapy. Antrodia cinnamomea (AC) a widely used edible medical fungus, exhibits hepatoprotective, anti-inflammatory and anticancer activities. In this study, we investigated whether combined treatment with the ethonolic extract of AC ameliorates
cachexia symptoms, especially muscle wasting, in lung
tumor-bearing mice treated with
chemotherapy. Our results revealed that
gemcitabine and
cisplatin-induced severe
body weight loss and skeletal muscle
atrophy in the mice with
cancer were greatly attenuated after AC extract administration. The protection may be attributed to the inhibition of skeletal muscle proteolysis by suppressing
myostatin and
activin release, muscle wasting-related FoxO3/MuRF-1/MAFbx signaling, proteasomal
enzyme activity, and pro-inflammatory
cytokine production. A significant decrease in
insulin-like growth factor 1 (IGF-1) expression and formation was observed in the atrophying muscle of the conventional
chemotherapy treatment group (CGC), and this decrease was markedly reversed by AC treatment. Additionally, the
anorexia, intestinal injury and dysfunction that occurred in the CGC group were mitigated by AC extract. Taken together, these results demonstrated that the AC extract has a protective effect against
chemotherapy-induced
muscle atrophy mainly by attenuating muscle proteolysis, pro-inflammatory
cytokine production, and
anorexia, and activating IGF-1-dependent
protein synthesis.