Soyasapogenol B prevents sarcopenia by increasing skeletal muscle mass and function through the Sirt1/PGC-1α and PI3K pathway

Sarcopenia, caused by aging, is characterized by the reduction of muscle mass and function. In this study, we investigated the effects of soyasapogenol B on skeletal muscle and the underlying mechanisms to determine its potential as a prevention for sarcopenia. Soyasapogenol B, a natural triterpenoid found in soybeans, has biological effects that inhibit cancer, inflammation, and obesity; however, its effects on skeletal muscle remain unclear and require further investigation. C57/BL6 mice were fed soyasapogenol B for 8 weeks, after which skeletal muscle mass, function, and protein analysis for muscle synthesis and exercise mimetics were evaluated. The mechanism of skeletal muscle improvement by soyasapogenol B was identified through in vitro experiments. Soyasapogenol B increased the weight of the quadriceps and gastrocnemius muscles, grip strength, and running endurance. It also enhanced oxidative muscle fiber switching, mitochondrial enzyme complex, and mitochondria biogenesis through the Sirt1/PGC-1α pathway. Soyasapogenol B increased myogenic differentiation and protein synthesis, through the PI3K pathway. The upregulation of mitochondrial biogenesis and myogenic differentiation by soyasapogenol B was attenuated by treatment with EX-527, a SIRT1 inhibitor, and LY294002, a PI3K inhibitor. Molecular docking analyses showed that soyasapogenol B has the potential to directly bind to Sirt1. In conclusion, soyasapogenol B increased skeletal muscle mass, skeletal muscle strength and endurance by activating the Sirt1 and PI3K pathways. Thus, by promoting protein synthesis and mitochondrial biogenesis, soyasapogenol B could be a potential prevention option for sarcopenia.