An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats

• An intergated serum and urinary metabonomic to study osteoporosis has been proposed.
• The mechanism of Gushudan relies on regulating multiple metabolic pathways.
• The potential biomarkers associated with osteoporosis have been identified.

Gushudan, a Chinese compound formulation based on the theory of traditional Chinese medicine and desgined to treat osteoporosis. However, its intergated intervention effective mechanism in vivo is not well understood. In this study, an intergated serum and urinary metabonomic strategy based on UPLC-MS technique have been developed to increase the understanding of the metabolism characters of osteoporosis and to investigate the holistic therapeutic efficacy of Gushudan on prednisolone-induced osteoporosis rat model. Principle component analysis (PCA) was utilized to identify differences in metabolic profiles of rats in the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group and clear separation was achieved among three groups. Furthermore, 17 potential biomarkers from urine and 10 potential biomarkers from serum were identified, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has therapeutic effects on rat with osteoporosis via the regulation of multiple metabolic pathways. It’s worth mentioning that some new biomarkers associated with osteoporosis such as 3-methoxydopa, 2,8-digydroxyadenine have been discovered in this study for the first time. This study provides a useful approach to get insight into the intergated metabonomic mechanism of prednisolone-induced osteoporosis and to assess the efficacy of Gushudan on osteoporotic rats. The work also shows that the metabonomics method is a promising tool in the efficacy and mechanism research of traditional Chinese compound medicines.