Husain Islam, Abdulrahman Balkisu, Dale Olivia R, Katragunta Kumar, Idrisi Mantasha, Gurley Bill J, Ali Zulfiqar, Avula Bharathi, Chittiboyina Amar G, Khan Ikhlas A, Ujah Frederick Oduh, Khan Shabana I
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, United States.
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, United States; Department of Biochemistry and Molecular Biology, Faculty of Life Sciences, Federal University Dutsin-Ma, Dutsin-Ma, Katsina State, 821101, Nigeria.
J Ethnopharmacol. 2025 Jan 13;339:119142. doi: 10.1016/j.jep.2024.119142. Epub 2024 Nov 19.
Phyllanthus amarus is ethnomedicinally used to treat gallbladder stones, kidney stones and chronic liver diseases. P. amarus is gaining popularity as an ingredient in many botanical dietary supplements.
To evaluate the interaction of P. amarus extract and its lignans with human xenobiotic sensing receptors (PXR and AhR) and their downstream genes.
Activation of PXR and AhR was measured by reporter gene assays. Gene expression analysis was performed in hepatic (HepG2) and intestinal (LS174T) cells by RT-PCR. CYP inhibition assays were carried out in baculosomes. The inhibitory effect on the ABC transporters (P-gp and BCRP) was investigated via rhodamine-123 and Hoechst 33342 uptake assays in Caco-2 and MDR-MDCK cells. Effect on CYP3A4 and CYP1A2 enzyme activity was measured in primary human hepatocytes.
P. amarus extract and its lignans activated AhR and PXR in respective reporter cells. Tested extract and lignans significantly increased CYP3A4 mRNA but inhibited CYP3A4 enzyme activity when tested in primary human hepatocytes and CYP3A4-specific baculosomes. In contrast, increased CYP1A2 mRNA was associated with increased CYP1A2 enzyme activity in hepatocytes. No inhibition of CYP1A2 activity was detected in baculosomes. A weak inhibitory effect on ABC-transporters was observed.
Results suggest that overconsumption of P. amarus or P. amarus-containing botanical supplements may change CYP homeostasis which could alter the pharmacokinetics of substrate drugs, thereby elevating the risk of herb-drug interactions (HDIs) when taken concomitantly with conventional medications. Further studies are warranted to strengthen the clinical relevance of these findings.
苦味叶下珠在民族医学中用于治疗胆结石、肾结石和慢性肝病。苦味叶下珠作为许多植物性膳食补充剂的一种成分正变得越来越受欢迎。
评估苦味叶下珠提取物及其木脂素与人源外源性物质感应受体（孕烷X受体和芳烃受体）及其下游基因的相互作用。
通过报告基因检测法测定孕烷X受体和芳烃受体的激活情况。通过逆转录聚合酶链反应在肝（HepG2）细胞和肠（LS174T）细胞中进行基因表达分析。在杆状病毒体中进行细胞色素P450抑制试验。通过在Caco-2细胞和多药耐药性犬肾细胞中进行罗丹明-123和 Hoechst 33342摄取试验，研究对ABC转运蛋白（P-糖蛋白和乳腺癌耐药蛋白）的抑制作用。在原代人肝细胞中测定对细胞色素P450 3A4和细胞色素P450 1A2酶活性的影响。
苦味叶下珠提取物及其木脂素在各自的报告细胞中激活了芳烃受体和孕烷X受体。当在原代人肝细胞和细胞色素P450 3A4特异性杆状病毒体中进行测试时，受试提取物和木脂素显著增加了细胞色素P450 3A4 mRNA，但抑制了细胞色素P450 3A4酶活性。相反，在肝细胞中细胞色素P450 1A2 mRNA增加与细胞色素P450 1A2酶活性增加相关。在杆状病毒体中未检测到对细胞色素P450 1A2活性的抑制作用。观察到对ABC转运蛋白有微弱的抑制作用。
结果表明，过量食用苦味叶下珠或含苦味叶下珠的植物性补充剂可能会改变细胞色素P450的稳态，这可能会改变底物药物的药代动力学，从而在与传统药物同时服用时增加草药-药物相互作用的风险。有必要进一步开展研究以加强这些发现的临床相关性。
