| Objective To explore the mechanism of Jintiange (JTG) in preventing and treating osteosarcopenia (OS) based on the Akt/NF-κB/Bak signaling pathway. Methods In the pharmacophore model part, high performance liquid chromatography (HPLC) was used to determine the components of JTG. The pharmacophore model analysis of the obtained components was carried out. In the part of animal experiment, 60 6-month-old female SPF SD rats were randomly divided into Control group, Sham operation group, OS group, OS+JTG group, and OS+E2 group. Rats in the Sham group or the model group were performed Sham or OVX, respectively. One week after the operation, the rats in the model group were intraperitoneally injected with dexamethasone for two consecutive weeks. After 3 months of modeling, rats in the drug intervention group were intragastrically administered with JTG or E2 aqueous solution. Rats in the other groups were intragastrically administered with equal volume of normal saline. After gavage for 3 months, rats in each group were tested for forelimb grip, body composition, whole body and local bone mineral density, distal femur bone microstructure, proteins related to Akt/NF-κB/Bak signaling pathway, etc. Results Seventeen kinds of amino acids in JTG were identified using HPLC. The pharmacophore model found that these 17 amino acids might prevent and treat OS by regulating PI3K-Akt and apoptosis signaling pathways. Animal experiments found that JTG significantly improved the phenotypic characteristics of OS rats’ forelimb grip, whole body skeletal muscle mass index, whole body and local bone mineral density, and bone microstructure of the distal femur. JTG significantly increased the protein expression of p-Akt and NF-κB in gastrocnemius of OS rats, and inhibited the protein expression of pro-apoptotic protein Bak and muscle atrophy-related protein Fbx32. Conclusion JTG has the effect of preventing and treating OS, and its mechanism may be related to the activation of Akt/NF-κB/Bak signaling pathway. |