基于速效救心丸对 CYP450 酶和转运体的影响评价潜在的药物-草药相互作用。

Evaluation of potential herb-drug interactions based on the effect of Suxiao Jiuxin Pill on CYP450 enzymes and transporters.

机构信息

Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

出版信息

J Ethnopharmacol. 2021 Nov 15;280:114408. doi: 10.1016/j.jep.2021.114408. Epub 2021 Jul 10.

DOI:10.1016/j.jep.2021.114408

PMID:34252529

Abstract

ETHNOPHARMACOLOGY RELEVANCE

Suxiao jiuxin pill (SJP) is a Chinese medical drug with anti-inflammatory, anti-apoptotic, and vasodilatory function. It is widely used in combination with other drugs for the treatment of coronary heart disease (CHD) and angina. Nevertheless, the effect of SJP on Cytochrome P450 (CYP450) enzymes and transporters' activity related to drug metabolism is rarely studied.

OBJECTIVE

The aim of this study was to investigate the effect of SJP on the activity of drug-metabolizing enzyme CYP450 and transporters.

MATERIALS AND METHODS

Human primary hepatocytes were used in present study. Probe substrates of CYP450 enzymes were incubated in human liver microsomes (HLMs) with and without SJP while IC values were calculated. The inhibitory effect of SJP on the activity of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 was evaluated. The inducing effect of SJP on the activity of CYP1A2, 2B6 and 3A4 was accessed. The inhibition of SJP on human OATP1B1 was investigated through cell-based assay. The inhibition of SJP on human MDR1 and BCRP was also estimated by means of the vesicles assay.

RESULTS

The results showed that the SJP under the concentration of 1000 μg/mL could inhibit the activity of CYP1A2, 2B6, 2C19, and 3A4, with IC values of 189.7, 308.2, 331.2 and 805.7 μg/mL, respectively. There was no inhibitory effect found in the other 3 liver drug enzyme subtypes. In addition, SJP showed no induction effect on CYP1A2, 2B6 and 3A4, however it had a significant inhibitory effect on human-derived OATP1B1 at the concentration of 100 and 1000 μg/mL, with the IC value of 21.9 μg/mL. Simultaneously, the SJP inhibited BCRP at high concentration of 1000 μg/mL but did not affect human MDR1.

CONCLUSIONS

Based on these research results above, it is suggested that the SJP can affect some of the CYP450 enzymes and transporters' activity. When used in combination with related conventional drugs, potential herb-drug interactions should be considered.

摘要

民族药理学相关性

速效救心丸（SJP）是一种具有抗炎、抗凋亡和血管扩张作用的中药。它被广泛与其他药物联合用于治疗冠心病（CHD）和心绞痛。然而，SJP 对细胞色素 P450（CYP450）酶和与药物代谢相关的转运体活性的影响很少被研究。

目的

本研究旨在探讨 SJP 对药物代谢酶 CYP450 及转运体活性的影响。

材料与方法

本研究采用人原代肝细胞。在有和没有 SJP 的情况下，将 CYP450 酶的探针底物孵育在人肝微粒体（HLM）中，计算 IC 值。评估 SJP 对 CYP1A2、2B6、2C8、2C9、2C19、2D6 和 3A4 活性的抑制作用。评估 SJP 对 CYP1A2、2B6 和 3A4 活性的诱导作用。通过细胞基础测定法研究 SJP 对人 OATP1B1 的抑制作用。通过囊泡测定法评估 SJP 对人 MDR1 和 BCRP 的抑制作用。

结果

结果表明，浓度为 1000μg/mL 的 SJP 可抑制 CYP1A2、2B6、2C19 和 3A4 的活性，IC 值分别为 189.7、308.2、331.2 和 805.7μg/mL。在其他 3 种肝药物酶亚型中未发现抑制作用。此外，SJP 对 CYP1A2、2B6 和 3A4 没有诱导作用，但在 100 和 1000μg/mL 浓度下对人源 OATP1B1 有显著抑制作用，IC 值为 21.9μg/mL。同时，SJP 在高浓度 1000μg/mL 时抑制 BCRP，但不影响人 MDR1。