Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P‐gp In Vitro

Abstract

Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy and safety of Tripterygium wilfordii Hook F for CKD in Mainland China: A systematic review and meta‐analysis

“…Based on the data from the included studies, 0.5 to 1.5 mg·kg −1 ·day −1 of TwHF is recommended in future clinic application with less toxicity. Some researches also had attempted the following approaches to decrease its toxicity: (a) modify structure of its bioactive substances; (b) combine compounds reasonably; (c) purify its extracts; (d) optimize its extraction methods; and (e) change its formulations and administration methods (Hewitson, Ignatova, Ye, Chen, & Sutherland, 2009;Li et al, 2017;Nan, Zheng, & Xu, 2015;Shao et al, 2006;Tang & Zuo, 2012;Yuan et al, 2015;Zhang et al, 2014a;Zhang et al, 2016).…”

Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy

“…According to reports, TW has gastrointestinal reactions, liver damage, menstrual disorders, reproductive problems, adverse skin reactions, hematological events, cardiovascular events and nephrotoxicity ( Zhang C. et al, 2016 ; Brown, 2017 ). Therefore, researchers should devote themselves to finding bioactive substances with safe doses and modifying their structures; reasonable combination of drugs; purifying their extracts; optimizing extraction methods; changing their dosage forms and administration methods, reduce the toxicity, so as to make TW better serve the clinic ( Shao et al, 2006 ; Hewitson et al, 2009 ; Tang and Zuo, 2012 ; Zhang et al, 2014 ; Yuan et al, 2015 ; Zhang B. et al, 2016 ; Li Z. et al, 2017 ).…”

UPLC–MS/MS method for the simultaneous quantification of pravastatin, fexofenadine, rosuvastatin, and methotrexate in a hepatic uptake model and its application to the possible drug–drug interaction study of triptolide

“…This signified that DDIs might occur when TP and transporter-related substrate drugs were simultaneously administered, which may aggravate or reduce liver damage. For instance, a study on TP combined with glycyrrhetinic acid to reduce its toxicity was reported (Li et al, 2017).…”