Key Research Laboratory of Gynecology, Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.
Department of The Public Experiment Platform, Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7633-7640. doi: 10.3892/mmr.2017.7559. Epub 2017 Sep 20.
Methotrexate (MTX) is a widely used immunosuppressant and anticancer agent with high toxicity. Smilax glabra Rhizoma (SGR) has the effect of detoxification and immunoregulation, and has been used as both food and folk medicine in many countries. Co‑administration of MTX and SGR occurs in several diseases. However, whether they work synergistically or are incompatible remains unknown. In the present study, MTX was administrated to rats alone or combined with SGR. Blood and tissue samples were collected at designated times. The concentrations of MTX were determined by high‑performance liquid chromatography. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detected the gene expression. SGR decreased the AUC0‑t and Cmax of MTX by 44.5 and 48.2%, but in a tissue‑dependent manner. The total exposure of MTX was significantly decreased in the small intestine, stomach, plasma, and kidney by 61.6, 34.7, 63.3 and 46.1%, respectively, but was increased in the lung and spleen by 82.9 and 21.0%, respectively. RT‑qPCR demonstrated that SGR increased the mean P‑glycoprotein (gp) mRNA expression in the small intestine 2.54 times, but had a marginal effect on the expression of organic anion transporting polypeptide 2, and organic anion transporter (OAT)1 and OAT2. These results suggested that SGR affects the pharmacokinetics of MTX in a tissue‑dependent manner by affecting P‑gp, and the clinical effect of co‑administration depended on the disease site.
甲氨蝶呤（MTX）是一种广泛应用的免疫抑制剂和抗癌药物，具有很高的毒性。菝葜具有解毒和免疫调节作用，已在许多国家被用作食品和民间药物。MTX 和菝葜在多种疾病中联合使用。然而，它们是协同作用还是不兼容仍不清楚。在本研究中，单独给予 MTX 或与菝葜联合给予 MTX 处理大鼠。在指定时间采集血液和组织样本。采用高效液相色谱法测定 MTX 浓度。采用反转录定量聚合酶链反应（RT-qPCR）检测基因表达。菝葜使 MTX 的 AUC0-t 和 Cmax 分别降低了 44.5%和 48.2%，但呈组织依赖性。MTX 的总暴露量在小肠、胃、血浆和肾脏中分别显著降低了 61.6%、34.7%、63.3%和 46.1%，而在肺和脾脏中分别增加了 82.9%和 21.0%。RT-qPCR 表明，菝葜使小肠中的平均 P-糖蛋白（gp）mRNA 表达增加了 2.54 倍，但对有机阴离子转运多肽 2、有机阴离子转运体（OAT）1 和 OAT2 的表达仅有轻微影响。这些结果表明，菝葜通过影响 P-gp 以组织依赖性方式影响 MTX 的药代动力学，联合用药的临床效果取决于疾病部位。
