National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, United States.
Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, College Park, Maryland 20740, United States.
J Agric Food Chem. 2023 May 17;71(19):7521-7534. doi: 10.1021/acs.jafc.2c07912. Epub 2023 May 3.
Ginger is currently one of the most popular herbs commonly added to diverse foods, beverages, and dietary supplements. We evaluated the ability of a well-characterized ginger extract, and several of its phytoconstituents, to activate select nuclear receptors as well as modulate the activity of various cytochrome P450s and ATP-binding cassette (ABC) transporters because phytochemical-mediated modulation of these proteins underlies many clinically relevant herb-drug interactions (HDI). Our results revealed ginger extract activated the aryl hydrocarbon receptor (AhR) in AhR-reporter cells and pregnane X receptor (PXR) in intestinal and hepatic cells. Among the phytochemicals investigated, ()-6-gingerol, dehydro-6-gingerdione, and (6,8)-6-gingerdiol activated AhR, while 6-shogaol, 6-paradol, and dehydro-6-gingerdione activated PXR. Enzyme assays showed that ginger extract and its phytochemicals dramatically inhibited the catalytic activity of CYP3A4, 2C9, 1A2, and 2B6, and efflux transport capabilities of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Dissolution studies with ginger extract conducted in biorelevant simulated intestinal fluid yielded ()-6-gingerol and 6-shogaol concentrations that could conceivably exceed cytochrome P450 (CYP) IC values when consumed in recommended doses. In summary, overconsumption of ginger may disturb the normal homeostasis of CYPs and ABC transporters, which in turn, may elevate the risk for HDIs when consumed concomitantly with conventional medications.
姜是目前最受欢迎的草药之一，常被添加到各种食物、饮料和膳食补充剂中。我们评估了一种特征明确的姜提取物及其几种植物成分激活特定核受体的能力，以及调节各种细胞色素 P450 和 ATP 结合盒（ABC）转运蛋白的活性的能力，因为植物化学物质对这些蛋白的调节是许多临床上相关的草药-药物相互作用（HDI）的基础。我们的结果表明，姜提取物在 AhR 报告细胞中激活了芳香烃受体（AhR），在肠和肝细胞中激活了孕烷 X 受体（PXR）。在所研究的植物化学物质中，()-6-姜辣素、脱氢-6-姜二酮和(6,8)-6-姜二醇激活了 AhR，而 6-姜辣素、6-对甲氧基姜辣素和脱氢-6-姜二酮激活了 PXR。酶测定表明，姜提取物及其植物化学物质显著抑制了 CYP3A4、2C9、1A2 和 2B6 的催化活性，以及 P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）的外排转运能力。在生物相关模拟肠液中进行的姜提取物溶解研究得出的（)-6-姜辣素和 6-姜辣素浓度，在推荐剂量下食用时，可能超过细胞色素 P450（CYP）IC 值。总之，过量食用姜可能会扰乱 CYP 和 ABC 转运蛋白的正常体内平衡，从而在与常规药物同时使用时增加发生 HDI 的风险。
