Plasma metabolic profiling analysis of Cortex Periplocae-induced cardiotoxicity based on UPLC/Q-TOF-MS

Cortex Periplocae is a well-known form of traditional medicine with its unique cardiotonic action, anti-tumor activity and immune regulation effect. However, improper use of Cortex Periplocae often leads to cardiac toxicity, which in the most severe cases can even be life-threatening. Biochemical tests and histopathological examinations are primary methods for clinical trials. However, such approaches are time-consuming, lack specificity and have low sensitivity, which can easily lead to negative results in studies. Therefore, a more scientific and systematic evaluation of Cortex Periplocae cardiotoxicity is particularly important. In this study, we established a method that combines metabonomics with trend analysis of a gavage concentration series to find cardiac toxicity biomarkers of Cortex Periplocae. We created rat cardiotoxicity models, in which the toxicity was caused by Cortex Periplocae. We collected data from rat plasma samples based on metabonomics using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Multiple statistical analyses, such as principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples to screen potential cardiotoxicity biomarkers and metabolic pathways. Compared with the control group, after 7 days administration, the pathological sections showed cardiac toxicity. Moreover, some metabolites in the body changed significantly. Receiver operating characteristic curve (ROC) analysis showed that there are 11 metabolites related with cardiac toxicity, which play a role in "phenylalanine, tyrosine and tryptophan biosynthesis"; "phenylalanine metabolism"; "valine, leucine and isoleucine biosynthesis"; "glycerophospholipid metabolism" as well as "pantothenate and CoA biosynthesis". These metabolites can better explain the cardiotoxicity mechanism of Cortex Periplocae and provide a scientific and systematic method to evaluate the cardiotoxicity of Cortex Periplocae.