UHPLC–MS based metabolomics study of the ErZhi formula on skeletal muscle against osteosarcopenia focusing on energy metabolismOA

Background:The ErZhi formula(EZF)exhibits sound therapeutic effects onosteosarcopenia(OS).However,EZF''s therapeutic effects on skeletal muscles arerarely reported.This study explored the mechanism of EZF in skeletal muscle duringOS by integrating energy metabolism and metabolomics.Methods:After an ovariectomized rat model was established for 4 weeks,the ratswere subjected to a 12-week intervention of EZF and alendronate.The rats''bodyweight,gastrocnemius muscle mass,degree of myofiber fibrosis,and myofibercross-sectional area(CSA)were measured to evaluate the pathological state of thegastrocnemius muscle.The mitochondrial membrane potential and reactive oxygenspecies(ROS)levels were detected to assess mitochondrial function.Then,energymetabolite analysis and metabolomics were performed on the gastrocnemius muscle.Results:Compared to the model group,EZH increased CSA by 5.58%and decreasedmyofiber fibrosis by 15.11%.Notably,compared to the model group,EZH exhibiteda 52.66%increase in mitochondrial membrane potential and a 44.32%reductionin ROS levels.Starch and sucrose metabolism,insulin secretion,insulin resistance,and galactose metabolism were the most significantly affected pathways in energymetabolism.Thirty-five differential metabolites were found in the metabolomicsof the gastrocnemius muscle,and EZF could effectively inhibit the sphingolipidmetabolism pathway.Correlation analysis identified 13 differential metabolites thatwere significantly associated with skeletal muscle mass,ROS production,musclefibrosis,and mitochondrial function,suggesting that these metabolites may playimportant roles in the progression of skeletal muscle lesions.Conclusions:EZF alleviates OS by regulating skeletal muscle physiological indicators,mitochondrial function,and energy metabolism.