Abstract

As a classical traditional Chinese medicine, Wuzi-Yanzong-Wan (WZYZW) has been widely applied for several centuries to treat non-obstructive oligoasthenozoospermia (NOA), although its pharmacological mechanisms remain largely unknown. In this study, both plasma and urine metabolomics profiling was first analysed to explore the therapeutic mechanisms of WZYZW in NOA rats induced by removal of the unilateral testicle. Then, 106 identified compounds comprising WZYZW (our previous work), for which putative targets were discovered using systems pharmacology, were systematically analysed via mRNA microarrays to validate their putative targets. Finally, metabolomics-tested WZYZW-regulated metabolites were connected with validated targets using Spearman correlation analysis to further confirm the targets from a biological perspective. The results suggested that WZYZW plays key roles in modulating the concentrations of 18 metabolites in the metabolism of amino acids, lipids and so on, normalizing the metabolic phenotype and regulating metabolic disorders. Moreover, 27 targets of WZYZW (23 compounds) against NOA were validated, and metabolomics-tested metabolites were also found to be significantly related to these identified targets, suggesting that these targets and compounds are worthy of further research. This work offers the first systematic investigation of the efficacy of WZYZW against NOA and illustrates a practicable approach for explaining the molecular mechanisms of multicomponent drugs.