Leonurine-Standardized <i>Leonurus japonicus</i> Extract Promotes Recovery from Immobilization-Induced Muscle Atrophy via PI3K/Akt/mTOR Signaling in Mice

Muscle atrophy involves the progressive loss of muscle mass and function, often linked to aging, disease, or inactivity.Although Leonurus japonicus and its active compound, leonurine, possess antioxidant and anti-inflammatory properties, their potential to improve muscle mass remains unknown.This study investigated the recovery-promoting effects and underlying mechanisms of a leonurine-standardized water extract of L. japonicus (LJW) and leonurine on muscle atrophy.We hypothesized that LJW and leonurine would promote recovery from muscle atrophy by activating the PI3K/Akt/mTOR pathway and suppressing FoxO3a-mediated proteolysis.Atrophy was induced in mice via 1-week hindlimb immobilization, followed by daily oral administration of LJW (150 or 300 mg/kg) or leonurine (30 mg/kg) for 1 week.LJW and leonurine not only improved exercise capacity and grip strength but also increased muscle volume, muscle mass, and crosssectional area in the immobilized hindlimbs.At the molecular level, both treatments activated the mammalian target of rapamycin (mTOR) pathway for protein synthesis.They also increased forkhead box O3a (FoxO3a) phosphorylation and reduced FoxO3a-associated proteolytic markers, attenuating catabolic signaling by enhancing the phosphatidylinositol 3kinase (PI3K)/Akt pathway.Furthermore, molecular docking analysis suggested that leonurine potentially interacts with the PI3K protein.Additionally, treatments reduced total nuclear factor kappa B (NF-κB) protein levels, which was accompanied by the downregulation of tumor necrosis factor α and interleukin 6.Taken together, LJW and leonurine enhanced recovery from immobilization-induced muscle atrophy, indicating their potential as novel therapeutic agents against muscle wasting.