Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

作者：Wang Lijuan; Wang Changyuan; Peng Jinyong; Liu Qi; Meng Qiang; Sun Huijun; Huo Xiaokui; Sun Pengyuan; Yang Xiaobo; Zhen Yuhong; Liu Kexin^*

来源：Toxicology and Applied Pharmacology, 2014, 277(2): 146-154.

DOI：10.1016/j.taap.2014.03.013

• Dioscin
• Methotrexate
• Absorption
• Nuclear factor kappa-B
• Inhibitor kappa B-alpha

The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor K-B (NF-kappa B) activities in Caco-2 cells. Moreover, inhibitor kappa B-alpha (I kappa B-alpha) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-kappa B signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MIX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen.

• 出版日期2014-6-1
• 单位大连医科大学