School of Pharmacy and Health Sciences, International Medical University, 126 Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
J Ethnopharmacol. 2011 Jan 27;133(2):881-7. doi: 10.1016/j.jep.2010.11.026. Epub 2010 Nov 18.
Andrographis paniculata (AP), Centella asiatica (CA) and Orthosiphon stamineus (OS) are three popular herbs traditionally used worldwide. AP is known for the treatment of infections and diabetes and CA is good for wound healing and healthy skin while OS is usually consumed as tea to treat kidney and urinary disorders. Interaction of these herbs with human cytochrome P450 2C19 (CYP2C19), a major hepatic CYP isoform involved in metabolism of many clinical drugs has not been investigated to date.
In this study, the modulatory effects of various extracts and major active constituents of AP, CA and OS on CYP2C19 activities were evaluated.
S-mephenytoin, the CYP2C19 substrate probe, was incubated in the presence or absence of AP, CA and OS components. The changes in the rate of metabolite (hydroxymephenytoin) formation were subsequently determined by a high-performance liquid chromatography (HPLC)-based enzyme assay to characterize the modulatory effects.
Among the herbal extracts studied, AP ethanol extract and CA dichloromethane extract exhibited mixed type inhibition towards CYP2C19 with K(i) values of 67.1 and 16.4 μg/ml respectively; CA ethanol extract and OS petroleum ether extract competitively inhibited CYP2C19 activity (K(i)=39.6 and 41.5 μg/ml respectively). Eupatorin (a major active constituent of OS) was found to significantly inhibit CYP2C19 by mixed type inhibition (K(i)=7.1 μg/ml or 20.6 μM).
It was observed that AP, CA and OS inhibited CYP2C19 activity with varying potency. While weak inhibitory effect was observed with AP, moderate to strong inhibition was observed with CA dichloromethane extract and eupatorin, the major OS constituent. Therefore care should be taken when these CA and OS components are co-administered with CYP2C19 substrates (such as omeprazole, proguanil, barbiturates, citalopram, and diazepam).
穿心莲（AP）、积雪草（CA）和益智（OS）是三种在全球范围内广泛使用的流行草药。AP 以治疗感染和糖尿病而闻名，CA 对伤口愈合和健康皮肤有益，而 OS 通常作为茶来治疗肾脏和泌尿系统疾病。迄今为止，尚未研究这些草药与人类细胞色素 P450 2C19（CYP2C19）之间的相互作用，CYP2C19 是一种主要的肝 CYP 同工酶，参与许多临床药物的代谢。
本研究评估了 AP、CA 和 OS 的各种提取物和主要活性成分对 CYP2C19 活性的调节作用。
使用 S-美芬妥因（CYP2C19 底物探针），在存在或不存在 AP、CA 和 OS 成分的情况下进行孵育。随后通过高效液相色谱（HPLC）基于酶的测定来确定代谢物（羟基美芬妥因）形成速率的变化，以表征调节作用。
在所研究的草药提取物中，AP 乙醇提取物和 CA 二氯甲烷提取物对 CYP2C19 表现出混合抑制作用，K(i) 值分别为 67.1 和 16.4 μg/ml；CA 乙醇提取物和 OS 石油醚提取物竞争性抑制 CYP2C19 活性（K(i)=39.6 和 41.5 μg/ml 分别）。发现益智的主要活性成分 eupatorin 通过混合抑制显著抑制 CYP2C19（K(i)=7.1 μg/ml 或 20.6 μM）。
观察到 AP、CA 和 OS 以不同的效力抑制 CYP2C19 活性。AP 表现出较弱的抑制作用，CA 二氯甲烷提取物和益智的主要成分 eupatorin 表现出中等至强抑制作用。因此，当 CA 和 OS 成分与 CYP2C19 底物（如奥美拉唑、普罗喹酮、巴比妥类、西酞普兰和地西泮）共同给药时，应谨慎。
