RESUMEN
Skeletal muscle atrophy, which is characterized by diminished muscle mass, strength, and function, is caused by malnutrition, physical inactivity, aging, and diseases. Korean mint (Agastache rugosa Kuntze) possesses various biological functions, including anti-inflammatory, antioxidant, anticancer, and antiosteoporosis activities. Moreover, it contains tilianin, which is a glycosylated flavone that exerts antioxidant, anti-inflammatory, antidiabetic, and neuroprotective activities. However, no studies have analyzed the inhibitory activity of A. rugosa extract (ARE) and tilianin on muscle atrophy. Thus, the present study investigated the potential of ARE and tilianin on muscle atrophy and their underlying mechanisms of action in C2C12 myotubes treated with tumor necrosis factor-α (TNF-α). The results showed that ARE and tilianin promoted the phosphatidylinositol 3-kinase/protein kinase B pathway, thereby activating mammalian target of rapamycin (a protein anabolism-related factor) and its downstream factors. Moreover, ARE and tilianin inhibited the mRNA expression of muscle RING-finger protein-1 and atrogin-1 (protein catabolism-related factors) by blocking Forkhead box class O3 translocation. ARE and tilianin also mitigated inflammatory responses by downregulating nuclear factor-kappa B expression levels, thereby diminishing the expression levels of inflammatory cytokines, including TNF-α and interleukin-6. Additionally, ARE and tilianin enhanced the expression levels of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, these results suggest that ARE and tilianin are potential functional ingredients for preventing or improving muscle atrophy.
RESUMEN
Sarcopenia, age-related muscle atrophy, weakening muscle strength, and exercise capacity, generally accompany imbalances in protein metabolism. Chrysanthemum morifolium Ramat. extract (CME) and its active compound, isochlo-rogenic acid A (IcA), have been reported to have anti-oxidative, anti-diabetic, and neuroprotective effects. However, the roles of CME and IcA in the regulation of muscle protein turnover-related signaling pathways to attenuate sarcopenia have not been explored. In this study, we investigated CME and IcA based regulation of protein turnover in synthesizing muscle in vitro and in vivo. At the molecular level, CME and IcA promoted phosphorylation of PI3K/Akt and mTOR pathways, which stimulate synthesis of muscle proteins, and suppressed FoxO3a and E3 ubiquitin ligases during protein degrada-tion. In vivo, CME and IcA increased grip strength, exercise capacity, muscle mass and volume, and cross-sectional area of myofibers in middle-aged C57BL/6J mice. These results suggest that CME and IcA may have roles as functional food supplements for delaying sarcopenia by enhancing muscle mass recovery and function.
