Jingui Shenqi Wan alleviates bone loss induced by primary osteoporosis by inhibiting osteoblast pyroptosis.

Abstract

OBJECTIVE: The primary objective of this study was to elucidate the underlying pharmacological mechanisms by which Jingui Shenqi Wan (JGSQW) alleviates postmenopausal osteoporosis (PMOP). Through a systematic investigation, we sought to identify the specific molecular pathways through which JGSQW modulates the progression of PMOP, thereby providing a scientific basis for its clinical application. METHODS: We established an ovariectomized (OVX) mouse model to simulate estrogen deficiency-induced PMOP. Initially, micro-CT imaging and Alcian blue hematoxylin/orange G (ABH/OG) staining were employed to assess the effects of JGSQW on bone microarchitecture and bone mass preservation. Immunohistochemistry (IHC) was then utilized to evaluate the expression of osteogenic markers, including Osterix (OSX), Runx2, and Osteopontin (OPN). Additionally, Tartrate - Resistant Acid Phosphatase (TRAP) staining was performed to visualize and quantify osteoclasts. We further investigated the potential role of JGSQW in modulating the pyroptosis pathway. RESULTS: JGSQW effectively alleviates the destruction of bone microstructure and the loss of bone mass caused by estrogen deficiency, an effect that appears to be mediated by promoting osteogenesis. Additionally, JGSQW significantly downregulates the expression of GSDMD in osteoblasts and mitigates the abnormal release of inflammatory factors, thereby maintaining the normal functional activities of osteoblasts. CONCLUSION: JGSQW may effectively mitigate the progression of estrogen deficiency-induced PMOP by inhibiting the dysregulated activation of osteoblast pyroptosis.