通过细胞色素450抑制试验评估Synacinn™与个体生物标志物的药草-药物相互作用。

Evaluation of Herb-Drug Interaction of Synacinn™ and Individual Biomarker through Cytochrome 450 Inhibition Assay.

作者信息

Ab Rahman Nur Syukriah, Abd Majid Fadzilah Adibah, Abd Wahid Mohd Effendy, Zainudin Ain Nabihah, Zainol Siti Nurazwa, Ismail Hassan Fahmi, Wong Tet Soon, Tiwari Nirbhay Kumar, Giri Sanjeev, Bhargava Vijaya

机构信息

Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia.

Department of Bioprocess Engineering, Faculty of Chemical & Energy Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia.

出版信息

Drug Metab Lett. 2018;12(1):62-67. doi: 10.2174/1872312812666180314112457.

DOI:10.2174/1872312812666180314112457

PMID:29542427

Abstract

BACKGROUND

SynacinnTM contains five standardized herbal extracts of Orthosiphon Stamineus (OS), Syzygium polyanthum (SZ), Curcuma xantorrizza (CX), Cinnamomum zeylanicum (CZ) and Andrographis paniculata (AP) and is standardized against phytochemical markers of rosmarinic acid, gallic acid, curcumin, catechin and andrographolide respectively. This herbal medicine has been used as health supplement for diabetes. SynacinnTM is recommended to be consumed as supplement to the diabetic drugs. However, herb-drug interaction of SynacinnTM polyherbal with present drugs is unknown.

METHODS

This study was designed to investigate the effect of SynacinnTM and its individual biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography- tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron).

RESULTS

Result showed that SynacinnTM at maximum concentration (5000 µg/ml) 100% inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively. Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and CYP2C19 (72%) at 10µM.

CONCLUSION

Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.

摘要

背景

SynacinnTM含有五种标准化草药提取物，分别为猫须草（OS）、多花山竹（SZ）、郁金（CX）、锡兰肉桂（CZ）和穿心莲（AP），并分别以迷迭香酸、没食子酸、姜黄素、儿茶素和穿心莲内酯的植物化学标记物为标准。这种草药已被用作糖尿病的健康补充剂。建议将SynacinnTM作为糖尿病药物的补充剂服用。然而，SynacinnTM多草药与现有药物的药草-药物相互作用尚不清楚。

方法

本研究旨在研究SynacinnTM及其单个生物标志物对药物代谢酶（CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4（咪达唑仑）、CYP3A4（睾酮））的影响，通过细胞色素P450抑制试验评估其药草-药物相互作用潜力。本研究使用液相色谱-串联质谱（LC-MS/MS），使用探针底物，以人肝微粒体针对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4（咪达唑仑）和CYP3A4（睾酮）进行。

结果

结果显示，SynacinnTM在最大浓度（5000μg/ml）时100%抑制CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4（咪达唑仑）和CYP3A4（睾酮）。所测定的IC50值分别为CYP 1A2、2B6、2C8、2C9、2C19、2D6、3A4（咪达唑仑）和3A4（睾酮）的0.23、0.60、0.47、0.78、1.23、0.99、1.01和0.91mg/ml。同时，除姜黄素在10μM时对所有测试的CYP450显示出抑制作用（CYP2C8为91%、CYP2C9为81%、CYP2C19为72%）外，所有单个生物标志物对所有测试的CYP450均无、较少或中等抑制作用。