In Vitro Assessment of CYP-Mediated Drug Interactions for Kinsenoside, an Antihyperlipidemic Candidate.

Shaheed Rehman,Hye Yoo,Yongbo Xue,Yonghui Zhang,Zengwei Luo,Min Choi,Guangming Yao,In Kim

doi:10.3390/molecules21060800

Abstract

Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the potential for kinsenoside-drug interactions. Kinsenoside was tested at different concentrations of 0.1, 0.3, 1, 3, 10, 30, and 100 µM in human liver microsomes. The c Cktail probe assay based on liquid chromatography-tandem mass spectrometry was conducted to measure the CYP inhibitory effect of kinsenoside. Subsequently, the metabolism profiles of amlodipine and lovastatin in human liver microsomes were analyzed following co-incubation with kinsenoside. The concentration levels of the parent drug and the major metabolites were compared with the kinsenoside-cotreated samples. The effect of kinsenoside was negligible on the enzyme activity of all the CYP isozymes tested even though CYP2A6 was slightly inhibited at higher concentrations. The drug-drug interaction assay also showed that the concomitant use of kinsenoside has a non-significant effect on the concentration of lovastatin or amlodipine, and their major metabolites. So, it was concluded that there is almost no risk of drug interaction between kinsenoside and CYP drug substrates via CYP inhibition.

Highlights

Kinsenoside (3-R-3-β-D-glucopyranosyloxybutanolide) is the principal bioactive constituent of Anoect chilus formosanus, an important ethnomedicinal plant in Asian countries, primarily Taiwan and China [1,2,3]
The inhibitory effects of kinsenoside on cytochrome P450 (CYP) enzymes were investigated in human liver microsomes
The results indicated that kinsenoside has a negligible inhibitory effect on six CYP isozymes, while CYP2A6-specific metabolite formation (i.e., 7-OH-coumarin) was slightly inhibited in a concentration-dependent manner

Summary

Introduction

Kinsenoside (3-R-3-β-D-glucopyranosyloxybutanolide) is the principal bioactive constituent of Anoect chilus formosanus, an important ethnomedicinal plant in Asian countries, primarily Taiwan and China [1,2,3]. Studies have reported that kinsenoside exhibits a variety of pharmacological actions, including antihyperlipidemic, antihyperglycemic, anti-inflammatory, antioxidant, immune-stimulating, anti-osteoporosis, hepatoprotective, and vasculoprotective effects [1,2,3,4,5,6,7,8,9]. All of these pharmacological activities and drug-likeness make kinsenoside a promising drug candidate, and further investigation is needed to test its efficacy and safety. Their co-administration with conventional medicines can have life-threatening

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