Hot melt extruded Kyungohkgo attenuates skeletal muscle atrophy by downregulating the FOXO3a/MuRF-1/atrogin-1 axis

Skeletal muscle atrophy is a common and debilitating consequence of chronic diseases and aging, yet effective treatment alternatives remain limited. Kyungohkgo (KOG), a traditional oriental medicine, has been shown to have potential therapeutic benefits for muscle health, but its therapeutic efficacy is restricted caused by poor bioavailability. This study aimed to enhance both the bioavailability and efficacy of KOG by applying hot-melt extrusion (HME) processing, creating a modified formulation to evaluate its effectiveness in treating skeletal muscle atrophy. Network pharmacology analysis was conducted to illustrate the relationships between the traditional medicine KOG and sarcopenia. Both in vivo and in vitro models of skeletal muscle atrophy were employed to compare the effects of conventional KOG and HME-processed KOG (HOG3). HME processing yielded an optimized formulation, HOG3, characterized by nanoscale particle size and a marked increase in minor ginsenoside content. In this study, HOG3 showed significantly higher ginsenoside levels than KOG, with Rg3, compound K, and Rh2 increasing approximately 19-, 78-, and 18-fold, respectively. In cellular and animal models, HOG3 outperformed KOG in preserving muscle mass, reducing muscle degradation markers, and decreasing collagen deposition. HOG3 administration was associated with decreased expression level of FOXO3a, MuRF-1, and atrogin-1. Overall, these findings show that HOG3 indicates enhanced protective effects against skeletal muscle atrophy and is associated with modulation of downstream molecular markers related to muscle degradation.