The Integration Methodology of Metabolomics and Bioinformatics to Investigate the Mechanism of the Jiawei Erzhi Formula in Treating Postmenopausal Osteoporosis Based on the Kidney‐Bone Axis

ABSTRACT Postmenopausal osteoporosis (PMOP) is becoming a global health concern. The “kidney‐bone axis” provides a novel way to treat bone diseases by nourishing the kidney. The Jiawei Erzhi Formula (JWEZF) is used widely in clinics. Although research indicates the JWEZF has kidney‐protective and anti‐osteoporosis effects, the study based on the “kidney‐bone axis” of JWEZF to treat PMOP remains insufficient. Bioinformatics, an emerging field, can be combined with network pharmacology to obtain drug action prediction targets. Such targets can then be combined with the differential metabolites obtained by metabolomics to reveal the mechanism of drug action more accurately from the two levels of metabolites and targets. The analysis of the alterations in endogenous small molecule metabolites in the kidneys and urine of PMOP rats was done using metabolomics. In addition, bioinformatics and network pharmacology research were performed concurrently to forecast possible targets for the therapeutic action of JWEZF, including the kidney deficiency component. Finally, the primary metabolic pathways through which JWEZF functions were identified by an integrated metabolomics and bioinformatics investigation, and these pathways were validated using western blot. JWEZF was implicated in the regulation of five metabolic pathways, according to renal and urine metabolomics. Forty targets were suggested for JWEZF treatment of kidney deficiency and PMOP. According to the findings of the combined analysis, JWEZF mainly has therapeutic effects by influencing tryptophan and sphingolipid metabolism. Further to the western blot details, JWEZF regulates important enzymes in the pathways involved in tryptophan and sphingolipid metabolism pathways. JWEZF is effective in treating PMOP by nourishing the kidneys. The paper provides a new view on treating PMOP based on the kidneys.