Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA.
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA.
Molecules. 2017 Nov 23;22(12):2049. doi: 10.3390/molecules22122049.
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a reflection of increase in calcein-AM uptake. Additionally, the enzyme induction potential of the extracts was assessed through the modulation of PXR activity in HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA. Significant inhibition of CYP activity ( < 10 µg/mL) was observed with the following herbs: [CYP2C9, 3A4 and CYP2D6]; [CYP2C9]; [CYP2C9 and CYP2C19]; [CYP2C19, CYP2C9 and CYP3A4]; [CYP2C19 and CYP3A4]. Extracts of four herbs (, , and ) exhibited significant inhibition of P-gp with values (µg/mL) of 17 ± 1, 16 ± 0.4, 26 ± 1, and 24 ± 1, respectively. In addition, four herbs (, , and ) showed a >two-fold increase in induction in PXR activity. These findings suggest that these herbs may be capable of eliciting herb-drug interactions if consumed in high quantities with concomitant use of conventional therapies.
七种在西非常用于治疗疟疾的药用植物被选中，通过一系列体外方法评估草药-药物相互作用的潜力。使用重组 CYP 酶（CYP1A2、CYP2A6、CYP2B6、CYP2C9、CYP2C19、CYP2D6 和 CYP3A4）进行荧光细胞色素 P450（CYP）测定，以评估甲醇提取物对 CYP 代谢活性的影响。其次，使用荧光底物 calcein-AM 在 MDCK-II 和 hMDR1-MDCK-II 细胞中评估提取物对 P-糖蛋白（P-gp）的抑制作用。calcein-AM 摄取的增加反映了 P-gp 活性的抑制。此外，通过在瞬时转染 pSG5-PXR 和 PCR5 质粒 DNA 的 HepG2 细胞中调节 PXR 活性来评估提取物的酶诱导潜力。以下草药对 CYP 活性有显著抑制作用（<10μg/mL）：[CYP2C9、3A4 和 CYP2D6]；[CYP2C9]；[CYP2C9 和 CYP2C19]；[CYP2C19、CYP2C9 和 CYP3A4]；[CYP2C19 和 CYP3A4]。四种草药（、、和）的提取物对 P-gp 表现出显著抑制作用，其 值（μg/mL）分别为 17±1、16±0.4、26±1 和 24±1。此外，四种草药（、、和）表现出 PXR 活性的两倍以上增加。这些发现表明，如果与常规疗法同时大量使用这些草药，它们可能会引起草药-药物相互作用。
