National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA.
Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA.
J Diet Suppl. 2023;20(4):582-601. doi: 10.1080/19390211.2022.2050875. Epub 2022 Mar 18.
The dried roots and rhizomes of species ( and ), commonly known as licorice, have long been used in traditional medicine. In addition, two other species, and are also considered "licorice" in select markets. Currently, licorice is an integral part of several botanical drugs and dietary supplements. To probe the botanicals' safety, herb-drug interaction potential of the hydroethanolic extracts of five species and their key constituents was investigated by determining their effects on pregnane X receptor, aryl hydrocarbon receptor, two major cytochrome P450 isoforms (CYP3A4 and CYP1A2), and the metabolic clearance of antiviral drugs. All extracts enhanced transcriptional activity of PXR and AhR (>2-fold) and increased the enzyme activity of CYP3A4 and CYP1A2. The highest increase in CYP3A4 was seen with (4-fold), and the highest increase in CYP1A2 was seen with (18-fold) and (16-fold). Among the constituents, glabridin, licoisoflavone A, glyasperin C, and glycycoumarin activated PXR and AhR, glabridin being the most effective (6- and 27-fold increase, respectively). Licoisoflavone A, glyasperin C, and glycycoumarin increased CYP3A4 activity while glabridin, glyasperin C, glycycoumarin, and formononetin increased CYP1A2 activity (>2-fold). The metabolism of antiretroviral drugs (rilpivirine and dolutegravir) was increased by (2.0 and 2.5-fold) and its marker compound glycycoumarin (2.3 and 1.6-fold). The metabolism of dolutegravir was also increased by (2.8-fold) but not by its marker compound, glabridin. These results suggest that licorice and its phytochemicals could affect the metabolism and clearance of certain drugs that are substrates of CYP3A4 and CYP1A2.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2050875 .
种（ 和 ）的干燥根和根茎，通常被称为甘草，长期以来一直被用于传统医学。此外，另外两个种， 和 ，在某些市场也被认为是“甘草”。目前，甘草是几种植物药和膳食补充剂的组成部分。为了探究这些植物的安全性，本文研究了五种 种植物及其关键成分的水醇提取物对孕烷 X 受体、芳香烃受体、两种主要细胞色素 P450 同工酶（CYP3A4 和 CYP1A2）以及抗病毒药物代谢清除率的影响，以评估其草药-药物相互作用的潜力。所有提取物均能增强 PXR 和 AhR 的转录活性（>2 倍），并增加 CYP3A4 和 CYP1A2 的酶活性。 中 CYP3A4 的增加最为明显（增加 4 倍），而 CYP1A2 的增加最为明显（增加 18 倍）和 （增加 16 倍）。在这些成分中，甘草素、甘草异黄酮 A、甘草次酸 C 和甘草香豆素激活了 PXR 和 AhR，其中甘草素的效果最为显著（分别增加 6 倍和 27 倍）。甘草异黄酮 A、甘草次酸 C 和甘草香豆素增加了 CYP3A4 的活性，而甘草素、甘草次酸 C、甘草香豆素和芒柄花素增加了 CYP1A2 的活性（>2 倍）。抗逆转录病毒药物（利匹韦林和多替拉韦）的代谢分别被 （增加 2.0 倍和 2.5 倍）和其标记化合物甘草香豆素（增加 2.3 倍和 1.6 倍）所增加。多替拉韦的代谢也被 （增加 2.8 倍）所增加，但不是其标记化合物甘草素。这些结果表明，甘草及其植物化学物质可能会影响某些药物的代谢和清除率，这些药物是 CYP3A4 和 CYP1A2 的底物。本文的补充数据可在 https://doi.org/10.1080/19390211.2022.2050875 上在线获取。
