A variety of beneficial pharmacological activities have been reported for dihydromyricetin (DMY), however, its oral bioavailability is poor and the intestinal absorption profiles of DMY remains unknown. The aim of this study was to investigate the uptake and transport mechanism of DMY in human intestinal Caco-2 cells. DMY was detected using a liquid chromatography-tandem mass spectrometry method. Several factors including time, concentration, pH, temperature and efflux transporters were systematically evaluated. DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, decreasing the pH from 8.0 to 6.0 markedly enhanced the DMY uptake, but didn't significantly affect its bidirectional transport. Efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein also influenced the DMY uptake and transport processes. This work details the uptake and transport characteristics of DMY and provides basis for future study. PRACTICAL APPLICATION This study elucidated the uptake and transport characteristics of dihydromyricetin (DMY). DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, pH affected DMY uptake but not its bidirectional transport. MRP2 and BCRP were involved in the uptake and transport of DMY, which hindered the absorption of DMY in the intestinal. Thus, the present study may provide useful information for designing DMY delivery systems and avoiding DMY-drug interactions.

中文翻译：

---

二氢杨梅素在人肠道 Caco-2 细胞中的摄取和转运机制

据报道，二氢杨梅素 (DMY) 具有多种有益的药理活性，但其口服生物利用度较差，且 DMY 的肠道吸收谱仍未知。本研究旨在探讨 DMY 在人肠道 Caco-2 细胞中的摄取和转运机制。使用液相色谱-串联质谱法检测 DMY。系统地评估了包括时间、浓度、pH、温度和外排转运蛋白在内的几个因素。DMY 很难被被动扩散机制吸收。DMY 的吸收和转运与时间和浓度有关。有趣的是，将 pH 从 8.0 降低到 6.0 会显着增强 DMY 的吸收，但不会显着影响其双向传输。外排转运蛋白，多药耐药蛋白2和乳腺癌耐药蛋白也影响了DMY的摄取和转运过程。这项工作详细介绍了 DMY 的吸收和运输特性，为未来的研究提供了基础。实际应用 本研究阐明了二氢杨梅素 (DMY) 的摄取和转运特性。DMY 很难被被动扩散机制吸收。DMY 的吸收和转运与时间和浓度有关。有趣的是，pH 影响 DMY 的吸收，但不影响其双向运输。MRP2和BCRP参与了DMY的摄取和转运，阻碍了DMY在肠道的吸收。因此，本研究可为设计 DMY 递送系统和避免 DMY-药物相互作用提供有用的信息。