UPLC-Q-TOF-MS/MS-based urine metabolomics studies on the toxicity and detoxication of Tripterygium wilfordii Hook. f. after roasting

• Published in: Journal of pharmaceutical and biomedical analysis 2023-09, Vol.234, p.115573-115573, Article 115573
• Main Authors: Chen, Shu, Liu, Li, Jiang, Hong-Xia, Sun, Qun, Zhang, Liang, Liu, Jian-Qun, Liu, Li-Fang
• Format: Article
• Language: English
• Subjects: Detoxication; Mechanism; Metabolomics; Roasting; Toxicity; Tripterygium wilfordii Hook. f
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2023.115573

Tripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW. [Display omitted] •The detoxification effect was linked to the reduction of alkaloids and celastrol.•Six endogenous metabolites were identified as common detoxification biomarkers.•Five endogenous metabolites were firstly reported as toxicity biomarkers.•Roasting reduced toxicit