Sophorae tonkinensis radix et rhizome-induced pulmonary toxicity: A study on the toxic mechanism and material basis based on integrated omics and bioinformatics analyses.

The root and rhizome of Sophora tonkinensis Gagnep. (ST) are widely used for the treatment of tonsillitis, sore throats, and heat-evil-induced diseases in traditional Chinese medicine. However, the clinical application of ST is relatively limited due to its toxicity. The mechanism and material basis of ST-induced pulmonary toxicity are still unclear. In the present research, integrated omics and bioinformatics analyses were used to investigate the toxic mechanism and material basis of ST in lung tissue. Proteomics and metabonomics were integrated to analyze the differentially expressed proteins and metabolites. Joint pathway analysis was used to analyze the significantly dysregulated pathways. PubChem and the Comparative Toxicogenomics Database were applied for the screen of toxic targets and compounds. Integrated omics revealed that 323 proteins and 50 metabolites were differentially expressed after treating with ST, out of which 19 proteins and 1 metabolite were significantly enriched in seven pathways. Bioinformatics showed that 15 compounds may indirectly affect the expression of 9 toxic targets of ST. Multiple toxic targets of ST-induced pulmonary injury were found in the study, whose dysregulation may trigger pulmonary cancer, dyspnea, and oxidative stress. Multiple compounds may be the toxic material basis in response to these effects.