Integrative investigation of Semen Strychni nephrotoxicity and the protective effect of Radix Glycyrrhizae by a UPLC-MS/MS method based cell metabolomics strategy in HEK 293t cell lysates

Abstract

Semen Strychni has anti-tumor, analgesic and anti-inflammatory angiogenesis effects, but the clinical use of Semen Strychni is limited by its potential nephrotoxicity. To investigate Semen Strychni nephrotoxicity and the protective effect of Radix Glycyrrhizae, a stable, parallel and repeatable cell metabolomics strategy was developed in this study. After treatment with Semen Strychni, cell morphology was changed, cell viability was decreased and 8 biochemical indexes were altered. Then the developed cell models were successfully applied for a cell metabolomics study. The Semen Strychni group samples were completely separated from the blank group samples in the score plots of PCA and PLS-DA models. Finally, a total of 10 putative biomarkers and 24 related metabolic pathways were screened. Among the 24 metabolic pathways, the taurine and nitrogen metabolic pathways were believed to have the most importance and significance, respectively. Based on the results, the possible mechanisms of Semen Strychni nephrotoxicity might be cellular component disruption, oxidative damage, metabolic waste accumulation and the disturbance of energy and ion transport systems. Meanwhile, the Radix Glycyrrhizae treatment group showed similar behaviors to the blank group in all assays, indicating the great protective effect of Radix Glycyrrhizae against Semen Strychni nephrotoxicity. This cell metabolomics strategy might contribute to investigating the possible nephrotoxic mechanisms of herb medicines and clinical therapies of protective herbs.