Integrated metabolomics and network toxicology to reveal molecular mechanism of celastrol induced cardiotoxicity
| Autor: | Tao He, Fuli Yuan, Chenning Zhang, Jianmei Huang, Yahong Chen, Qiang Wang, Chuanxin Liu, Wenxin Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Tripterygium Inflammation Toxicology medicine.disease_cause Cardiotoxins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics Western blot medicine Animals Rats Wistar Caspase Pharmacology Cardiotoxicity biology medicine.diagnostic_test Chemistry biology.organism_classification Triterpenes Rats 030104 developmental biology Celastrol 030220 oncology & carcinogenesis biology.protein Tripterygium wilfordii medicine.symptom Pentacyclic Triterpenes Oxidative stress Metabolic Networks and Pathways |
| Zdroj: | Toxicology and applied pharmacology. 383 |
| ISSN: | 1096-0333 |
| Popis: | Celastrol (CS), an active triterpene derived from traditional Chinese medicine Tripterygium wilfordii Hook. f, has been used to treat chronic inflammation, arthritis and other diseases. However, it has been reported that CS can trigger cardiotoxicity and the molecular mechanism of heart injury induced by CS is not clear. Considering the wide application of Tripterygium wilfordii Hook. f in clinics, it is necessary to develop an accurate and reliable method to assess the safety of CS, and to elucidate as much as possible the mechanism of cardiotoxicity induced by CS. In this study, Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics revealed clues to the mechanism of CS-induced heart injury. Palmitic acid significantly increased in plasma from CS-treated rats, and this increase resulted in oxidative stress response in vivo. Excessive ROS further activate TNF signaling pathway and caspase family, which were obtained from the KEGG enrichment analysis of network toxicology strategy. Protein expression level of caspase-3, caspase-8, bax were significantly increased by western blot. Q-PCR also showed the similar results as western blot. It means that apoptosis plays a key role in the process of celastrol induced cardiotoxicity. Blocking this signal axis may be a potential way to protect myocardial tissue. |
| Databáze: | OpenAIRE |
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