Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the “kidney governing bone” theory

BACKGROUND: Guzhi Zengsheng Zhitongwan (GZZSZTW) is an effective Chinese medicinal formulation for the treatment of osteoarthritis (OA) designed according to the “kidney governing bone” theory, which has been widely used as a golden guide for treating bone and cartilage diseases in traditional Chinese medicine. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney. METHODS: Preparation and quality control were performed as previously described. Since GZZSZTW is orally administered in the form of pills prepared in boiled water, the Chinese materia medica (CMM) mixture of this formula was extracted with distilled water by a reflux method and was then filtered through a 0.45-μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. The effects of GZZSZTW on gene expression and regulation of both kidney and bone tissues were investigated using a state-of-the-art RNA-seq technology. RESULTS: We demonstrated that GZZSZTW could enhance kidney function and suppress bone formation and resorption by modulating the activities of osteoblast and osteoclast, and might subsequently contribute to the inhibition of osteophyte formation during the process of OA. These effects might be achieved by the synergistic interactions of various herbs and their active components in GZZSZTW, which increased the expression levels of functional genes participating in kidney function, regulation, and repair, and then decreased the expression levels of genes involved in bone formation and resorption. Thus, our findings were consistent with the “kidney governing bone” theory, which has been widely used as a guide in clinical practice for thousands of years. CONCLUSIONS: This study has deepened the current knowledge about the molecular effects of GZZSZTW on bone and kidney regulation. Furthermore, this study might be able to provide possible strategies to further prevent and treat joint diseases by using traditional Chinese medicinal formulations following the “kidney governing bone” theory.