关键词： ATP, adenosine 5′ triphosphate CYP, cytochrome P450 Cytochrome P450 3A DMSO, dimethyl sulfoxide Drug−herb interaction EGFR, epidermal growth factor receptor FDA, Food and Drug Administration GEF, gefitinib G−6−P, glucose−6−phosphate G−6−PD, G−6−P dehydrogenase HER2, human epidermal growth factor receptor 2 HLM, human liver microsome HPLC, high-performance liquid chromatography Herbal extract IC50, half maximal inhibitory concentration Ki, inhibition constant LC/MS, liquid mass spectrometry NADP, nicotinamide adenine dinucleotide phosphate PDGFR, platelet−derived growth factor receptor RAF, Rapidly Accelerated Fibrosarcoma SOR, sorafenib TKI, tyrosine kinase inhibitor Tyrosine kinase inhibitor UGT, UDP-glucuronosyltransferase UV, ultraviolet VEGFR, vascular endothelial growth factor receptor

来  源：   DOI：10.1016/j.toxrep.2022.10.004   PDF(Pubmed)

Abstract：
Herbal products are widely used in cancer patients via co-administration with chemotherapy. Previous studies have demonstrated that pharmacokinetic interactions between herbs and anticancer drugs exist due to inhibition of drug-metabolizing enzymes, particularly cytochrome P450s (CYPs). The aim of this study was to determine the inhibitory effects of Andrographis paniculata, Curcuma zedoaria, Ganoderma lucidum, Murdannia loriformis and Ventilago denticulata extracts on the metabolism of gefitinib, lapatinib and sorafenib. The activities of CYP3A in human liver microsome on the metabolism of gefitinib, lapatinib and sorafenib in the absence and presence of Thai herbal extracts were assayed using high-performance liquid chromatography analysis. Curcuma zedoaria extract potently inhibited CYP3A-mediated lapatinib and sorafenib metabolism with IC50 values of 4.18 ± 3.20 and 7.59 ± 1.23 μg/mL, respectively, while the metabolism of gefitinib was strongly inhibited by Murdannia loriformis and Ventilago denticulata extracts with IC50 values of 7.53 ± 2.87 and 7.06 ± 1.23 μg/mL, respectively. Andrographis paniculata and Ganoderma lucidum extracts had less effect on the metabolism of the tested anticancers (IC50 values >10 μg/mL). In addition, kinetic analysis of the ability of Curcuma zedoaria extract to inhibit CYP3A-mediated metabolism of anticancer drugs was best described by the noncompetitive and competitive inhibition models with Ki values of 20.08 and 11.55 μg/mL for the metabolism of gefitinib and sorafenib, respectively. The present study demonstrated that there were potential pharmacokinetic interactions between tyrosine kinase inhibitors and herbal extracts.
摘要：
草药产品通过与化疗共同给药广泛用于癌症患者。以前的研究表明，由于抑制药物代谢酶，草药和抗癌药物之间存在药代动力学相互作用，特别是细胞色素P450（CYPs）。这项研究的目的是确定穿心莲的抑制作用，姜黄,灵芝,乌尔丹尼亚和文提物对吉非替尼代谢的影响,拉帕替尼和索拉非尼。人肝脏微粒体CYP3A活性对吉非替尼代谢的影响,在不存在和存在泰国草药提取物的情况下，拉帕替尼和索拉非尼使用高效液相色谱分析。姜黄提取物能有效抑制CYP3A介导的拉帕替尼和索拉非尼的代谢，IC50为4.18±3.20和7.59±1.23μg/mL，分别,而吉非替尼的代谢受到莫尔丹尼和文提拉提取物的强烈抑制，IC50值分别为7.53±2.87和7.06±1.23μg/mL，分别。穿心莲和灵芝提取物对所测试的抗癌剂的代谢影响较小(IC50值>10μg/mL)。此外,姜黄提取物抑制CYP3A介导的抗癌药物代谢的能力的动力学分析最好通过非竞争性和竞争性抑制模型描述，Ki值为20.08和11.55μg/mL的吉非替尼和索拉非尼的代谢，分别。本研究表明，酪氨酸激酶抑制剂和草药提取物之间存在潜在的药代动力学相互作用。
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