Influence of astragaloside IV on pharmacokinetics of triptolide in rats and its potential mechanism

Jian Gao,Xiangmin Zeng,Wei Zhao,Desheng Chen,Jing Liu,Ning Zhang,Xingliang Duan

doi:10.1080/13880209.2019.1702705

Jian Gao, Xiangmin Zeng + Show 5 more

Open Access

https://doi.org/10.1080/13880209.2019.1702705

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Abstract

Context It is common to combine two or more drugs in clinics in China. Triptolide (TP) has been used primarily for the treatment of inflammatory and autoimmune diseases. Astragaloside IV (AS-IV) has been applied with many other drugs, due to its various pharmacological effects. AS-IV and TP can be used together for the treatment of diseases in clinics in China. Objective This study investigates the effects of astragaloside IV (AS-IV) on the pharmacokinetics of TP in rats and its potential mechanism. Materials and methods The pharmacokinetics of orally administered triptolide (2 mg/kg) with or without AS-IV pre-treatment (100 mg/kg/day for 7 d) were investigated. Additionally, the effects of AS-IV on the transport of triptolide were investigated using the Caco-2 cell transwell model. Results The results indicated that when the rats were pre-treated with AS-IV, the C max of triptolide decreased from 418.78 ± 29.36 to 351.31 ± 38.88 ng/mL, and the AUC0-t decreased from 358.83 ± 19.56 to 252.23 ± 15.75 μg/h/L. The Caco-2 cell transwell experiments indicated that AS-IV could increase the efflux ratio of TP from 2.37 to 2.91 through inducing the activity of P-gp. Discussion and conclusions In conclusion, AS-IV could decrease the system exposure of triptolide when they are co-administered, and it might work through decreasing the absorption of triptolide by inducing the activity of P-gp.

Highlights

Triptolide (TP), a diterpenoid triepoxide, is a major pharmacological component isolated from Tripterygium wilfordii Hook F (Celastraceae) (TWHF) (Brinker and Raskin 2005), and it has been used primarily for the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and skin diseases (Cheng et al 2014; Li et al 2014)
Zhang et al (2016) have reported that Astragaloside IV (AS-IV) could induce the activity of P-gp, which might lead to drug–drug interactions when they are coadministered with other herbs or drugs that are P-gp substrates
Pre-treatment with AS-IV (100 mg/kg/ day for 7 d) in rats was associated with a significant decrease of AUC0–t compared with the control (p < 0.05)

Summary

Introduction

Triptolide (TP), a diterpenoid triepoxide, is a major pharmacological component isolated from Tripterygium wilfordii Hook F (Celastraceae) (TWHF) (Brinker and Raskin 2005), and it has been used primarily for the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and skin diseases (Cheng et al 2014; Li et al 2014). Based on its multiple biological activities and remarkable clinical performance, TP has attracted the attention of researchers and gained wide acceptance in the world in recent decades. Astragaloside IV (AS-IV) is one of the major active compounds of Radix Astragali. Zhang et al (2016) have reported that AS-IV could induce the activity of P-gp, which might lead to drug–drug interactions when they are coadministered with other herbs or drugs that are P-gp substrates. AS-IV and TP might be used together for the treatment of diseases in Chinese clinics, such as rheumatic diseases and diabetic nephropathy (Shi et al 2016). Many herb–drug interactions resulting from the concurrent use of herbal drugs with over-the-counter drugs may cause adverse reactions such as toxicity and treatment failure. There is an urgent need to investigate the potential for drug-drug interactions of TP

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