ArticleFrontiers in pharmacology2016
Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Protective role of autophagy in triptolide-induced apoptosis of TM3 Leydig cells.Journal of translational internal medicine · 2023Article
- Triptolide Induces Liver Injury by Regulating Macrophage Recruitment and Polarization via the Nrf2 Signaling Pathway.Oxidative medicine and cellular longevity · 2022Article
- Proteomics analysis reveals novel insights into the mechanism of hepatotoxicity induced byFrontiers in pharmacology · 2022Article
- The molecular pathogenesis of triptolide-induced hepatotoxicity.Frontiers in pharmacology · 2022Review
- DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures.Clinical epigenetics · 2021Article
- The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism.Frontiers in pharmacology · 2021Review
- Metabolic profiling of fatty acids inOpen life sciences · 2021Article
- Natural Products Targeting Liver X Receptors or Farnesoid X Receptor.Frontiers in pharmacology · 2021Review
- Sex, gut microbiome, and cardiovascular disease risk.Biology of sex differences · 2019Review
- Research Progress on the Animal Models of Drug-Induced Liver Injury: Current Status and Further Perspectives.BioMed research international · 2019Review
- Activation of natural killer T cells contributes to triptolide-induced liver injury in mice.Acta pharmacologica Sinica · 2018Article
- Mechanisms of Triptolide-Induced Hepatotoxicity and Protective Effect of Combined Use of Isoliquiritigenin: Possible Roles of Nrf2 and Hepatic Transporters.Frontiers in pharmacology · 2018Article
- Article
- Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.Frontiers in pharmacology · 2017Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook. f., exerts a unique bioactive spectrum of anti-inflammatory and anticancer activities. However, triptolide's clinical applications are limited due to its severe toxicities. Fatty liver toxicity occurs in response to triptolide, and this toxic response significantly differs between males and females. This report investigated the pathogenesis underlying the sex-related differences in the dyslipidosis induced by triptolide in rats. Wistar rats were administered 0, 150, 300, or 450 μg triptolide/kg/day by gavage for 28 days. Ultrastructural examination revealed that more lipid droplets were present in female triptolide-treated rats than in male triptolide-treated rats. Furthermore, liver triglyceride, total bile acid and free fatty acid levels were significantly increased in female rats in the 300 and 450 μg/kg dose groups. The expression of liver X receptor α (LXRα) and its target genes, cholesterol 7α-hydroxylase (CYP7A1) and Sterol regulatory element-binding transcription factor 1(SREBP-1), increased following triptolide treatment in both male and female rats; however, the female rats were more sensitive to triptolide than the male rats. In addition, the expression of acetyl-CoA carboxylase 1(ACC1), a target gene of SREBP-1, increased in the female rats treated with 450 μg triptolide/kg/day, and ACC1 expression contributed to the sex-related differences in the triptolide-induced dysfunction of lipid metabolism. Our results demonstrate that the sex-related differences in LXR/SREBP-1-mediated regulation of gene expression in rats are responsible for the sex-related differences in lipid metabolism induced by triptolide, which likely underlie the sex-related differences in triptolide hepatotoxicity. This study will be important for predicting sex-related effects on the pharmacokinetics and toxicity of triptolide and for improving its safety.
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