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.