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Updated: Dec 11, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice
Jie Zhao1, Cen Xie2, Kanglong Wang3
1Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Academy of Chinses Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China; School of Pharmaceutical Science, Hebei Medical University, Shijiazhuang, Hebei, China; Laboratory of Metabolism, National Cancer Institute, Bethesda, MD, USA.
Abstract:
Triptolide, a major active component of Triptergium wilfordii Hook. f, is used in the treatment of autoimmune disease. However, triptolide is associated with severe adverse reactions, especially hepatotoxicity, which limits its clinical application. To examine the underlying mechanism of triptolide-induced liver injury, a combination of dose- and time-dependent toxic effects, RNA-seq and metabolomics were employed. Triptolide-induced toxicity occurred in a dose- and time-dependent manners and was characterized by apoptosis and not necroptosis. Transcriptomics profiles of the dose-dependent response to triptolide suggested that PI3K/AKT, MAPK, TNFα and p53 signaling pathways were the vital steps in triptolide-induced hepatocyte apoptosis. Metabolomics further revealed that glycerophospholipid, fatty acid, leukotriene, purine and pyrimidine metabolism were the major metabolic alterations after triptolide exposure. Finally, acylcarnitines were identified as potential biomarkers for the early detection of triptolide-induced liver injury.
