OBJECTIVE: To evaluate the effect of aqueous extract of Atractylodes atractylodes Rhizoma (AME) in improving muscle atrophy in mice, and to explore its mechanism of action.
METHODS: We induced skeletal muscle atrophy in mice by simulating human unhealthy lifestyle habits and concurrently administered them with AME. The polysaccharide content in the AME was determined using a UV-Vis spectrophotometer. The contents of three primary pharmacologically active components in the AME were quantified via HPLC. Body composition analysis was conducted weekly on the mice, and the mass of hindlimb skeletal muscles was measured after six weeks of treatment. Histopathological analysis of the skeletal muscles was performed using hematoxylin and eosin (HE) staining to evaluate the effect of AME on muscle atrophy. Mice grip strength and endurance were measured to assess their motor abilities and skeletal muscle function. Mechanisms underlying the ameliorative effect of AME on skeletal muscle atrophy were explored using qPCR and immunofluorescence staining techniques.
RESULTS: The modeling method employing alternate-day feeding with high-fat high-sugar diet combined with hindlimb immobilization significantly reduced the body weight of model mice within two weeks (P < 0.0001). Administration of Atractylodis Macrocephalae Radix aqueous extract to mice for six weeks increased body weight, total lean mass, and fat mass (P < 0.01, P < 0.001, P < 0.001 respectively). It also augmented the wet weight of the quadriceps femoris, gastrocnemius, soleus, and tibialis anterior muscles (P < 0.001, P < 0.01, P < 0.05, P < 0.05 respectively), enlarged the cross-sectional area of gastrocnemius muscle fibers, and improved the pathological morphology of skeletal muscles. Additionally, it enhanced skeletal muscle function in mice, increasing grip strength and endurance (P < 0.05), and augmented hindlimb microcirculatory blood flow (P < 0.01). Serum creatinine levels in mice were increased (P < 0.001), and the expression levels of genes related to skeletal muscle proliferation and differentiation, including Myf5, MyoD, Myogenin, Mef2, and myosin, were upregulated, Trim63 and Fbxo32 were downregulated. Furthermore, the conversion of type I to type II muscle fibers in the soleus muscle was improved.
CONCLUSION: Long-term IF & HFHS dietary patterns combined with hind limb immobilization can decrease overall muscle mass in mice, leading to a transformation of slow muscle fibers to fast muscle fibers. AME can increase skeletal muscle mass, enhance muscle function, and resist the transformation of slow muscle fibers to fast muscle fibers by regulating the expression of myogenic markers.
