Glycyrrhiza uralensis extract improves dexamethasone-induced sarcopenia via regulating myostatin- and FoxO3a-mediated E3 ubiquitin ligase

Sarcopenia affects the skeletal muscle system and impairs physical activity. This study investigated the effects of Glycyrrhiza uralensis (GU) extract on ameliorating dexamethasone (DEX)-induced sarcopenia in C2C12 myoblasts and C57BL/6J mice. Initially, network pharmacology analysis determined the association between GU and DEX-induced sarcopenia and predicted potentially related signaling pathways. Subsequently, the protective effects of different GU extracts on DEX-induced damage in C2C12 myotubes were evaluated by cell viability assays and Jenner and Giemsa (J&G) staining. Finally, the GU extract screened in vitro was evaluated by body composition analysis, grip strength and endurance tests, serum analysis, histological analysis, and protein expression level analysis in DEX-induced C57BL/6J mice. Network pharmacology confirmed the correlation between GU and DEX-induced sarcopenia involving TNF, MSTN, and FoxO signaling pathways. In DEX-induced damaged myotubes, only GU water extract (GW) dose-dependently increased cell viability. J&G staining of GW-treated myotubes revealed that GW increased the cell fusion index, maturation index and myotube diameter, attenuating DEX-induced cell damage. Oral administration of GW at doses above 300 mg/kg/day restored lean body mass lost due to DEX and subsequently reduced body fat. GW also enhanced grip strength and endurance, reduced muscle tissue injury, and increased the cross-sectional area of muscle fibers in DEX-induced mice. GW reduced the inflammatory response by alleviating serum TNF-α levels and ultimately decreased E3 ubiquitin ligase (MAFbx and MuRF-1) by downregulating myostatin and promoting FoxO3a phosphorylation. These results suggest that GU inhibits muscle protein degradation and is a potential food and medicinal homolog for preventing or treating sarcopenia. [Display omitted] •Glycyrrhiza uralensis (GU) is a traditional herb with a food-medicinal congener.•GU ameliorates dexamethasone (DEX)-induced damage in C2C12 cells.•GU improves muscle mass and quality in DEX-induced mice.•GU improves DEX-induced sarcopenia through the mediation of myostatin and FoxO3a.