Saikokeishikankyoto extract alleviates muscle atrophy in KKAy mice

<jats:title>Abstract</jats:title><jats:p>Sarcopenic obesity is associated with increased visceral fat and decreased muscle mass, resulting in decreased insulin sensitivity, increased production of inflammatory cytokines, and oxidative stress. In this study, we first evaluated the effects of herbal medicines on the transcriptional activity of the Sirtuin 1 (<jats:italic>sirt1</jats:italic>) promoter in vitro as an indicator of their therapeutic effect. Our data suggested that hot water Saikokeishikankyoto (SKK) extracts increased <jats:italic>sirt1</jats:italic> transcriptional activity in vitro<jats:italic>,</jats:italic> identifying it as a candidate therapeutic for evaluation in the KKAy type 2 diabetic obesity mouse model. These in vivo evaluations revealed that SKK treatment increased the wet weight and muscle fiber content in cross sections of the gastrocnemius muscle (GA) and restored motor function in these animals. In addition, SKK treatment reduced tumor necrosis factor-α (TNFα) expression in the sera and suppressed <jats:italic>Atrogin1</jats:italic> and <jats:italic>MuRF1</jats:italic> transcription in the GA samples. This treatment also increased <jats:italic>sirt1</jats:italic> expression in these tissues. These results suggest that SKK inhibits skeletal muscle atrophy and improves motor function in KKAy mice by suppressing inflammation. In actual clinical practice, SKK is expected to inhibit muscle atrophy and improve motor dysfunction in sarcopenic obesity.</jats:p> <jats:p><jats:bold>Graphical abstract</jats:bold></jats:p>