Gan-Mai-Da-Zao-Tang attenuates age-induced skeletal muscle wasting and improves mitochondrial function in mice

Skeletal muscle is the largest organ of the human body. It affects body metabolism and cooperates with other organs to maintain various physiological functions. Gan-Mai-Da-Zao-Tang (甘麥大棗湯, gān mài dà zǎo tāng, GMDZ) is a traditional Chinese medicine consisting of licorice, wheat, and jujube. GMDZ is commonly used to treat anxiety and depression. Increasing evidence shows a correlation exists between sarcopenia and depression. Muscle wasting, particularly in older individuals, increases the risk of depressive symptoms. The study aims to explore the effects of GMDZ water extract (WE) on age-induced muscle wasting and mitochondrial dysfunction in 25-week-old and 82-week-old mice. Exercise capacity was assessed through locomotor activity, rotarod performance, and grid-hanging tests. Grip strength was measured to assess muscle strength, while histological analysis and immunofluorescence staining were used to evaluate muscle mass and myofiber cross-sectional area. Protein expression, mRNA, and ATP levels were determined using western blots, real-time PCR, and ATP bioluminescence assays. GMDZ-WE significantly improved motor performance, grip strength, muscle mass, and myofiber cross-sectional area in aging mice. These enhancements were associated with increased MyHC expression and the IGF-1R/Akt protein synthesis pathway in skeletal muscle. In addition, GMDZ-WE decreased age-related protein degradation and inflammatory signaling, enhanced mitochondrial biogenesis signaling, increased GSH levels, SOD activity, and reduced lipid oxidation in the skeletal muscle of aging mice. In conclusion, GMDZ-WE reduces age-related skeletal muscle wasting, motor impairment, oxidative stress, inflammation, and mitochondrial dysfunction, demonstrating anti-aging potential on skeletal muscles. • GMDZ-WE enhances protein synthesis and mitochondrial function in C2C12 myotubes. • GMDZ-WE increases muscle strength and motor function in aging mice. • GMDZ-WE regulates protein synthesis and degradation signaling in the skeletal muscle. • GMDZ-WE attenuates inflammatory and oxidative signaling in the skeletal muscle.