Zhuanggu Zhitong Capsule alleviates osteosarcopenia in rats by up-regulating PI3K/Akt/Bcl2 signaling pathway

Background and aims: Osteosarcopenia (OS), characterized by the coexistence of osteoporosis (OP) and sarcopenia (SP), is associated with high morbidity and mortality in the elderly. Nevertheless, its pathogenesis and treatment remain unclear. The aim of this study was to investigate the effect and mechanism of Zhuanggu Zhitong Capsule (ZGZT) in OS rats. Methods: All the related targets of OS, corresponding targets for bioactive ingredients of ZGZT, intersection targets of ZGZT against OS, and signaling pathways were predicted and analyzed by network pharmacology. Next, a rat OS model was established by ovariectomy (OVX) and injection of dexamethasone (DXM). Rats were then randomly divided into a Control group, a Sham operation group, an OS model group, an OS+ZGZT group, and an OS+E-2 group. The drug was given for 12 weeks. During treatment, body weight, forelimb grip and body composition were measured. In addition, bone mineral density (BMD) and micro CT were used to assess the left femur. After treatment, the left femur, left gastmcnemius, and left soleus, as well as uterus, liver, and kidney, were separated and analyzed using Histomorphology, Western blot, and quantitative real-time PCR (qRT-PCR). Results: ZGZT could effectively improve the phenotypes of OS by increasing forelimb grip strength, percentage lean mass of the whole body (SMI) or appendicular lean (RSMI), BMD, levels of bone formation markers, improving the microstructure of femur, and decreasing apoptotic rate in femur and gastrocnemius in OS rats by up-regulating PI3K/Akt/Bcl2 signal pathway. Conclusions: ZGZT may be a new treatment option for the prevention and treatment of OS.