Integrated targeted sphingolipidomics and transcriptomics explore the mechanism of efficacy and toxicity of Tripterygium glycosides tablets on delayed-type hypersensitivity model
10.16438/j.0513-4870.2018-0510
- VernacularTitle:基于靶向鞘脂组学和转录组学的雷公藤多苷片对迟发型超敏反应模型的量-效/毒机制初探
- Author:
Zhe WANG
1
;
Liang QU
1
;
Jin-lan ZHANG
1
;
Feng QU
1
;
Dan ZHANG
1
;
Miao LIN
1
;
Yu TANG
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
Tripterygium glycosides tablets;
sphingolipidomics;
transcriptomics;
efficacy;
toxicity;
biomarker
- From:
Acta Pharmaceutica Sinica
2018;53(11):1868-1878
- CountryChina
- Language:Chinese
-
Abstract:
Tripterygium glycosides tablets (TGT) have good immunosuppressive activity, but they can also significantly injure the liver and kidney and its mechanism is unclear. In this study, delayed-type hypersensitivity (DTH) Balb/c mouse were administrated with different doses of TGT. Then the changes of sphingolipids levels in live, kidney and plasma as well as the mRNA expression levels of their metabolic enzymes were studied by the integrated targeted sphingolipidomics and transcriptomics methods to reveal the mechanism of efficacy and toxicity of TGT. It was found that low dose of TGT could significantly decrease levels of total ceramide in the plasma, long chain sphingolipids and saturate sphingolipids in the liver and kidney, but increase them in the plasma, which were related to the efficacy mechanism of TGT. High dose of TGT can significantly increase levels of total ceramide, Cer(d18:1/18:0)-1-P, long chain sphingolipids and decrease saturation sphingolipids mechanism. TGT can also cause significant changes of mRNA expression levels of various sphingolipid metabolic enzymes in the liver and kidney, which were correspond to the changes of sphingolipid levels. The efficacy and toxicity of TGT were related to the regulation of these key enzyme expression levels. In conclusion, the efficacy and toxic mechanism of TGT were closely related to the sphingolipids metabolism. A variety of potential biomarkers were found and they can provide valuable information for the evaluation of the efficacy and toxicity of TGT.
