Zuogui Wan attenuates ovariectomy-induced osteoporosis via the GH/IGF1 axis and related pathways

Zuogui Wan (ZGW)—one of the classic Chinese formulas—is clinically used to treat osteoporosis (OP). The current investigation aimed to analyze the phytochemical profile of ZGW and to elucidate its mechanisms of action in counteracting OP induced by ovariectomy (OVX) in rats. The UPLC-MS/MS method was employed to determine the unique qualitative profile of the compounds. OVX rats were subjected to ZGW treatment for 12 weeks. Changes in body weight and bone protective effects were evaluated using various assays, including Vaginal smear assay, HE staining, Micro-CT imaging, and biomechanical testing. The related genes and proteins were validated using RT-qPCR, IHC, and Western blot. The UPLC-MS/MS analysis identified 2091 compounds, and the integral correction diagram showed 23 metabolites. ZGW treatment effectively ameliorated the diminished bone mineral density and compromised bone microstructures observed in OVX rats. Furthermore, ZGW administration to OVX rats increased bone tissue expression levels of RUNX2, BMP2, OSX, OC, and OPG. Moreover, ZGW administration in OVX rats restored the disturbed GH/IGF1 axis. Also, it activated PI3K/AKT signaling pathway and YAP/TAZ signaling pathway. ZGW may exert its anti-OP effects by regulating the GH/IGF1 axis and its related signaling pathways.