Efficacy of Ethyl Acetate Fraction of Cordyceps militaris for Cancer-Related Fatigue in Blood Biochemical and ¹ H-Nuclear Magnetic Resonance Metabolomic Analyses

This study investigated the adjuvant effects for anticancer and antifatigue of the combination of Cordyceps militaris extract with sorafenib. The 5 extracts of C militaris were obtained through hexane, chloroform, ethyl acetate, butanol, and water and were evaluated for anticancer growth activity. Among these extracts, ethyl acetate extract of C militaris showed the best tumor growth inhibitory activity and the adjuvant effects in combination with sorafenib. As a result of biochemical analysis with serum, the combination of ethyl acetate extract of C militaris with sorafenib showed the adjuvant effects both improving hepatic function and relieving cancer-related fatigue. In addition, ¹H-nuclear magnetic resonance-based metabolic profiling in liver tissues showed that the change of metabolism by ethyl acetate extract of C militaris with sorafenib was related with serum fatigue biomarkers. Therefore, the combination strategy such as ethyl acetate extraction of C militaris with sorafenib constitutes a promising therapeutic strategy in hepatocellular carcinoma, via the inhibition of cancer growth, the enhancement of liver function, as well as the alleviation of cancer-related fatigue.

Keywords: 1H-NMR metabolic profiling; Cordyceps militaris; cancer-related fatigue; ethyl acetate fraction; hepatocellular carcinoma; xenograft mouse model.