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

Drug metabolism letters Pub Date : 2018-01-01 DOI:10.2174/1872312812666180314112457

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

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引用次数: 9

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.

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

背景:SynacinnTM是由5种标准化的草药提取物组成，分别为正茎(OS)、多花参(SZ)、姜黄(CX)、zeylanicum (CZ)和穿心莲(AP)，并以迷迭香酸、没食子酸、姜黄素、儿茶素和穿心莲内酯为标准植物化学标记物。这种草药已被用作糖尿病的保健品。建议将synacintm作为糖尿病药物的补充。然而，synacintm多草药与现有药物的相互作用尚不清楚。方法:通过细胞色素P450抑制试验，研究synacintm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，并评价其与药物的相互作用潜力。本研究采用液相色谱-串联质谱(LC-MS/MS)技术进行，探针底物为人肝微粒体，针对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4(咪达唑仑)和CYP3A4(睾酮)。结果:结果显示synacintm在最大浓度(5000µg/ml)下100%抑制CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4(咪达唑仑)和CYP3A4(睾酮)。CYP 1A2、2B6、2C8、2C9、2C19、2D6、3A4(咪达唑仑)和3A4(睾酮)的IC50分别为0.23、0.60、0.47、0.78、1.23、0.99、1.01和0.91 mg/ml。同时，除姜黄素在10µM下对CYP2C8(91%)、CYP2C9(81%)和CYP2C19(72%)有抑制作用外，所有个体生物标志物对所有CYP450均无、低或中等抑制作用。结论:姜黄素可能是抑制synacintm对CYP2C8、CYP2C9和CYP2C19的活性成分。这表明synacintm可以与已知被所有被测CYP450酶代谢的药物分开服用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Drug metabolism letters Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

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期刊介绍： Drug Metabolism Letters publishes letters and research articles on major advances in all areas of drug metabolism and disposition. The emphasis is on publishing quality papers very rapidly by taking full advantage of the Internet technology both for the submission and review of manuscripts. The journal covers the following areas: In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites.