Zhang Zhen-Dong, Tao Qi, Qin Zhe, Liu Xi-Wang, Li Shi-Hong, Bai Li-Xia, Yang Ya-Jun, Li Jian-Yong
Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China.
Front Nutr. 2022 May 24;9:894117. doi: 10.3389/fnut.2022.894117. eCollection 2022.
Naringenin, a flavanone, has been reported for a wide range of pharmacological activities. However, there are few reports on the absorption, transport and antioxidant effects of naringenin. The study was to explore the uptake, transport and antioxidant effects of naringenin . Cell transmembrane resistance, lucifer yellow transmission rate, and alkaline phosphatase activity were used to evaluate the successful construction of cell model. The results showed that the absorption and transport of naringenin by Caco-2 cells were time- and concentration-dependent. Different temperatures (37 and 4°C) had a significant effect on the uptake and transport of naringenin. Verapamil, potent inhibitor of P-glycoprotein, significantly inhibit naringenin transport in Caco-2 cells. The results revealed that naringenin was a moderately absorbed biological macromolecule and can penetrate Caco-2 cells, mainly mediated by the active transport pathway involved in P-glycoprotein. At the same time, naringenin pretreatment could significantly increase the viability of HO-induced Caco-2 cells. Twenty four differential metabolites were identified based on cellular metabolite analysis, mainly including alanine, aspartate and glutamate metabolism, histidine metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, purine metabolism, arginine biosynthesis, citrate cycle, riboflavin metabolism, and D-glutamine and D-glutamate metabolism. We concluded that the transport of naringenin by Caco-2 cells is mainly involved in active transport mediated by P-glycoprotein and naringenin may play an important role in oxidative stress-induced intestinal diseases.
柚皮素是一种黄烷酮，已被报道具有广泛的药理活性。然而，关于柚皮素的吸收、转运和抗氧化作用的报道较少。本研究旨在探讨柚皮素的摄取、转运和抗氧化作用。采用细胞跨膜电阻、荧光素黄透过率和碱性磷酸酶活性来评估细胞模型的成功构建。结果表明，Caco-2细胞对柚皮素的吸收和转运具有时间和浓度依赖性。不同温度（37℃和4℃）对柚皮素的摄取和转运有显著影响。维拉帕米是P-糖蛋白的强效抑制剂，可显著抑制Caco-2细胞中柚皮素的转运。结果显示，柚皮素是一种中等吸收的生物大分子，可穿透Caco-2细胞，主要通过与P-糖蛋白相关的主动转运途径介导。同时，柚皮素预处理可显著提高过氧化氢诱导的Caco-2细胞的活力。基于细胞代谢物分析鉴定出24种差异代谢物，主要包括丙氨酸、天冬氨酸和谷氨酸代谢、组氨酸代谢、牛磺酸和低牛磺酸代谢、丙酮酸代谢、嘌呤代谢、精氨酸生物合成、柠檬酸循环、核黄素代谢以及D-谷氨酰胺和D-谷氨酸代谢。我们得出结论，Caco-2细胞对柚皮素的转运主要涉及由P-糖蛋白介导的主动转运，并且柚皮素可能在氧化应激诱导的肠道疾病中发挥重要作用。
