ArticleScientific reports2015
Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 49 citations in OpenAlex.
- SoloxoloneInternational journal of molecular sciences · 2025Article
- Preparation, Characterization, and In Vivo Evaluation of an Oral Triptolide Nanomatrix System for Rheumatoid Arthritis Therapy.Pharmaceutics · 2025Article
- Exploratory Study of Sex Differences in P-Glycoprotein Function at the Blood-Brain Barrier.Clinical and translational science · 2025Article
- The molecular pathogenesis of triptolide-induced hepatotoxicity.Frontiers in pharmacology · 2022Review
- Role ofBiomedical reports · 2021Article
- Review
- ATP-binding Cassette Transporters Substantially Reduce Estimates of ALDH-positive Cancer Cells based on Aldefluor and AldeRed588 Assays.Scientific reports · 2019Article
- The Effect of Triptolide in Rheumatoid Arthritis: From Basic Research towards Clinical Translation.International journal of molecular sciences · 2018Review
- Triptolide Induces Apoptosis Through Fas Death and Mitochondrial Pathways in HepaRG Cell Line.Frontiers in pharmacology · 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
- Critical Role of Hepatic Cyp450s in the Testis-Specific Toxicity of (5R)-5-Hydroxytriptolide in C57BL/6 Mice.Frontiers in pharmacology · 2017Article
- Shengjiang Xiexin Decoction Alters Pharmacokinetics of Irinotecan by Regulating Metabolic Enzymes and Transporters: A Multi-Target Therapy for Alleviating the Gastrointestinal Toxicity.Frontiers in pharmacology · 2017Article
- Article
- Inhibition of P-Glycoprotein and Multidrug Resistance-Associated Protein 2 Regulates the Hepatobiliary Excretion and Plasma Exposure of Thienorphine and Its Glucuronide Conjugate.Frontiers in pharmacology · 2016Article
- Mapping the Binding Site of the Inhibitor Tariquidar That Stabilizes the First Transmembrane Domain of P-glycoprotein.The Journal of biological chemistry · 2015Article
- Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook.Journal of drug targetingReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide (TP) is the major active principle of Tripterygium wilfordii Hook f. and very effective in treatment of autoimmune diseases. However, TP induced hepatotoxicity limited its clinical applications. Our previous study found that TP was a substrate of P-glycoprotein and its hepatobiliary clearance was markedly affected by P-gp modulation in sandwich-cultured rat hepatocytes. In this study, small interfering RNA (siRNA) and specific inhibitor tariquidar were used to investigate the impact of P-gp down regulation on TP-induced hepatotoxicity. The results showed that when the function of P-gp was inhibited by mdr1a-1 siRNA or tariquidar, the systemic and hepatic exposures of TP were significantly increased. The aggravated hepatotoxicity was evidenced with the remarkably lifted levels of serum biomarkers (ALT and AST) and pathological changes in liver. The other toxicological indicators (MDA, SOD and Bcl-2/Bax) were also significantly changed by P-gp inhibition. The data analysis showed that the increase of TP exposure in mice was quantitatively correlated to the enhanced hepatotoxicity, and the hepatic exposure was more relevant to the toxicity. P-gp mediated clearance played a significant role in TP detoxification. The risk of herb-drug interaction likely occurs when TP is concomitant with P-gp inhibitors or substrates in clinic.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.