Development and application of a comprehensive lipidomic analysis to investigate Tripterygium wilfordii-induced liver injury

Abstract

Lipid metabolic pathways play pivotal roles in liver function, and disturbances of these pathways are associated with various diseases. Thus, comprehensive characterization and measurement of lipid metabolites are essential to deciphering the contributions of lipid network metabolism to diseases or its responses to drug intervention. Here, we report an integrated lipidomic analysis for the comprehensive detection of lipid metabolites. To facilitate the characterization of untargeted lipids through fragmentation analysis, nine formulas were proposed to identify the fatty acid composition of lipids from complex MS (n) spectrum information. By these formulas, the co-eluted isomeric compounds could be distinguished. In total, 250 lipids were detected and characterized, including diacylglycerols, triacylglycerols, glycerophosphoethanolamines, glycerophosphocholines, glycerophosphoserines, glycerophosphoglycerols, glycerophosphoinositols, cardiolipins, ceramides, and sphingomyelins. Integrated with the targeted lipidomics, a total of 27 inflammatory oxylipins were also measured. To evaluate the aberrant lipid metabolism involved in liver injury induced by Tripterygium wilfordii, lipid network metabolism was further investigated. Results indicated that energy lipid modification, membrane remodeling, potential signaling lipid alterations, and abnormal inflammation response were associated with injury. Because of the important roles of lipids in liver metabolism, this new method is expected to be useful in analyzing other lipid metabolism diseases.

Metabolic alterations in triptolide‐induced acute hepatotoxicity

“…Lysophosphatidylcholine (LysoPC) is a class of substance from the glycerophospholipids and plays a vital role in various liver disease. In the present study, the level of LysoPC was significantly increased in mice from the triptolide treatment group, which was consistent with another report (Xie et al, ). Previously studies revealed that LysoPC was a strong proinflammatory mediator, which could lead to the release of arachidonic acid by activating phospholipase A2 in two signaling pathways.…”

“…A UPLC‐MS lipidomic analysis revealed that energy lipid modification, membrane remodeling, potential signaling lipid alterations and abnormal inflammation response were associated with Tripterygium wilfordii Hook. F (TWHF)‐induced liver injury (Xie et al, ). Recently, an ultra performance liquid chromatography‐electrospray ionisation‐time of flight mass spectrometry (UPLC‐ESI‐QTOFMS) urine metabolomic survey found that eight potential biomarkers associated with tryptophan, pantothenic acid and porphyrin were related to triptolide toxicity and licorice had potential protective therapeutic effects against such toxicity (Wang et al, ).…”

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

“…Over the past 20 years, metabolomics has been used in many fields, such as responses to toxicology (Shi et al, ; Xie, Zhou, et al, ), nutrition (Guasch‐Ferre, Bhupathiraju, & Hu, ), disease diagnosis (Bujak et al, ; Li et al, ) and mechanism of drug action (Du et al, ; Wishart, ). Metabolomics is ideally positioned to address the challenges of toxicology in the twenty‐first century, as it provides accurate knowledge of disturbed biochemical pathways related to the extent of the toxic insult and its underlying mechanisms (Ramirez et al, ).…”

“…Indeed, the metabolic features of AF related to pathological phenomena may result in the discovery of new biomarkers that may improve clinical management of numerous conditions (Feng et al, ). Metabolomics has been widely applied in research on disease diagnosis (Bujak, Struck‐Lewicka, Markuszewski, & Kaliszan, ), drug action mechanism (Du et al, ; Wishart, ) and toxicity (Shi et al, ; Xie, Zhou, et al, ) during the past decades. Therefore, metabolomics may also be the most suitable strategy for evaluating the safety of CMs during pregnancy.…”

“…Metabolomics has been widely applied in research on disease diagnosis (Bujak, Struck-Lewicka, Markuszewski, & Kaliszan, 2015), drug action mechanism (Du et al, 2015;Wishart, 2016) and toxicity (Shi et al, 2016;Xie, Zhou, et al, 2016) during the past decades.…”