Agastache rugosa Extract Combined With Voluntary Wheel Exercise Affects the Improvement of Skeletal Muscle Homeostasis in Aged C57BL/6J Mice

OBJECTIVES: This study aimed to investigate the beneficial effects of Agastache rugosa (AR) combined with wheel running exercise on maintaining muscle homeostasis in aged skeletal muscle. METHODS: Male 38-week-old C57BL/6J mice were divided into five groups (n = 8/group): control (CON), Low-dose AR-treated (ARL, 100 mg/kg/day), High-dose AR-treated (ARH, 200 mg/kg/day), exercise (EXC), and EXC + ARH (EXH) group. After 2 weeks of acclimation period, AR-treated groups were fed AR extract by oral administration for 4 weeks. The daily voluntary wheel running (VWR) distance was recorded using a counter machine. In the gastrocnemius (GAS) muscle sample, muscle homeostasis-related genes and protein were analyzed by qPCR and western blotting, respectively. RESULTS: The weight of GAS in ARH and EXH increased significantly, compared to CON (p < 0.05). qPCR analysis showed that AR and exercise affected both oxidative and glycolytic muscle fibers. mRNA levels of Myh7 and Myh1 in EXH were remarkably higher than in CON (p < 0.05). Skeletal muscle atrophy (Atrogin-1 and MuRF-1) and hypertrophy (myogenin) related genes were up-regulated in EXC compared to CON (p < 0.05). Meanwhile, EXH dramatically down-regulated Atrogin-1 and MuRF-1 and up-regulated <> (p < 0.05). Western blotting analysis indicated that the hypertrophy-related protein p70S6 showed high levels in both exercise groups, but there was no statistically significant difference. In contrast, atrophy-related protein FOXO3a and MuRF-1 levels were remarkably lower in the EXC and EXH (p < 0.05). CONCLUSIONS: Taken together, this study demonstrated that AR with VWR exercise enhanced muscle homeostasis via regulation of skeletal muscle protein synthesis and degradation markers in aged hind-limb muscles. In conclusion, AR could be a promising candidate for maintaining muscle homeostasis and further alleviating sarcopenia. FUNDING SOURCES: This work was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (2012M3A9C4048761).