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      UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice

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          Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 June 2017
          : 15
          : 6
          : 474-480
          1Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
          2State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China
          3Key Laboratory of Modern Preparation of Traditional Chinese Medicines, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
          4Department of Surgery, Medical University of South Carolina, Charleston, SC 29466, USA
          Author notes
          *Corresponding author: LI Song-Lin, Tel/Fax: 86-25-85639640, E-mail: songlinli64@ ; LIU Li-Fang, Tel/Fax: 86-25-86185136, E-mail: liulifang69@

          ΔThese authors contributed to the work equally.

          These authors have no conflict of interest to declare.

          Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 81160541
          Award ID: 81373946
          Funded by: Health Department of Jiangxi Province
          Award ID: 2011A143
          This work was supported by the National Natural Science Foundation of China (Grant Nos. 81160541 and 81373946), the Project of Health Department of Jiangxi Province (Grant No. 2011A143), and the priority academic program development of Jiangsu higher education institutions (PAPD).


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