title: Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine.
abstract: Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2 mmol/L, 0.4 mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis. A "supervised" Support Vector Machine (SVM) study was used to optimize and verify the reliability of these biomarkers. In these biomarkers, all biomarkers, including carnitine, acetylcarnitine, lysoPC(16:0), proline, glutamic acid, pyroglutamic acid, leucine, pantothenic acid, tryptophan, indoleacrylic acid and citric acid, revealed a downward trend with the increase of dosage. Moreover, pathway analysis showed that these metabolites were associated with amino acid metabolism, energy metabolism and sphingolipid metabolism, which contributes to a further understanding of the toxicity mechanism of Corex Periplocae and its clinical safety. Additionally, we demonstrate that an UPLC-Q-TOF/MS-based metabolomic approach is a powerful tool and provides a promising approach for assessing the toxicity of traditional Chinese medicine and drug safety screening.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Aizhu
authors.initials: A
authors.lastname: Li
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Xie
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. Electronic address: yaowufenxi001@sina.com.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000596:Amino Acids; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism*; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D004734:Energy Metabolism / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D013058:Mass Spectrometry / Q000379:methods; D008516:Medicine, Chinese Traditional / Q000009:adverse effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012503:Saponins / Q000009:adverse effects*; D060388:Support Vector Machine
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D012503:Saponins; C502381:periplocin
keywords: Biomarkers; Cardiotoxicity; Metabolomics; Periplocin; SVM; UPLC-Q-TOF/MS