Naringenin Prevents Immobility and Loss of Muscle Function Caused by Cancer Cachexia in Mice

Objectives: Cancer cachexia, a progressive wasting of adipose and skeletal muscle, frequently occurs in cancer patients and is responsible for up to 20% of cancer related deaths. Many cancer therapies neglect treating reductions in physical activity and muscle function, which are associated with increased risk of death. Naringenin is a phytochemical found in citrus fruits that has anti-inflammatory and anticancer activities and may promote physical activity and preserve muscle function. This study investigated whether naringenin could significantly improve locomotor activity and muscle function in mice with cancer cachexia. Methods: Mice (16 male, CD2F1) were implanted with electronic telemetry transmitters prior to starting diets to continuously monitor locomotor activity. When mice were seven-to-eight weeks old, they were fed a semi-purified AIN 93-G diet supplemented with 2wt% naringenin (NAR) or without (CON) starting two weeks before being inoculated with colon-26 adenocarcinoma cells. Prior to inoculation and prior to sacrifice, muscle function was assessed using forelimb and all-limb grip strength, and the Aurora 1300A in vivo system to determine maximal torque during dorsiflexion. Results: Tumor bearing (NAR) mice had 14.6% higher cumulative locomotor activity counts, and significantly higher activity counts during the last three light phases before sacrifice (7740 vs 4940 P=0.047, 7230 vs 3538 P=0.006, 4217 vs 3244 P=0.015) compared to CON mice. NAR mice, versus CON mice, had significantly higher gastrocnemius weight (0.976 vs 0.831%TFM, P=0.039), and higher forelimb (4.28 vs 3.55gf, P=0.042) and all-limb (10.25 vs 8.76gf, P=0.018) grip strength. Maximal torque was not significantly different between NAR and CON diet groups. Conclusions: Tumor bearing (NAR) mice had significantly higher locomotor activity, grip strength, and gastrocnemius weight compared to tumor bearing (CON) mice. Further research will explore the mechanisms by which naringenin has positive effects on cancer cachexia, including effects on systemic inflammation, skeletal muscle gene expression and proteins implicated in muscle wasting. Funding Sources: This project was supported by the Center for Advanced Functional Foods Research and Enterprise.