Transcellular transport of aconitine across human intestinal Caco-2 cells

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• 作者：Cuiping Yang ^{yangsophia76@hotmail.com} ; Zheng Li ^{lizh2524@126.com} ; Tianhong Zhang ^{wdzth@sina.com} ; Fei Liu ^{liufeipharm@163.com} ; Jinxiu Ruan ^{ruanjx1936@yahoo.com.cn} ; Zhenqing Zhang ; ^{zhangzhenqingpharm@163.com} ; ^{zqzhang55@yahoo.com}
• 关键词：Aconitine ; Caco-2 cells ; P-glycoprotein (P-gp) ; pH-dependent carrier-mediated transport
• 刊名：Food and Chemical Toxicology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：57
• 期：Complete
• 页码：195-200
• 全文大小：783 K

文摘

Aconitine (AC) is a highly toxic compound present in plants of the genus Aconitum. The transcellular transport mechanism of AC was investigated using Caco-2 cells. The flux of AC was time- and concentration-dependent in both apical-to-basolateral and the reverse direction. The efflux of AC was more than two-fold that in the opposite direction. The influx of AC was temperature-, pH- and Na⁺-dependent. Glucose markedly decreased the absorption of AC. However, the efflux of AC was temperature- and pH-dependent, but Na⁺-independent. Cyclosporin A and verapamil, both inhibitors of P-glycoprotein (P-gp), significantly decreased the efflux of AC. In addition, MK-571, an inhibitor of multidrug resistance-associated protein 2 (MRP2), exhibited the same trend but to a lesser extent. These results indicate that both the influx and efflux of AC across Caco-2 monolayers were through an active process. A pH-dependent carrier-mediated transport system was the major absorption mechanism and a sodium-dependent glucose transporter may be involved. The active efflux of AC across Caco-2 cells was mediated mainly by ABC-transporter P-gp. It is involved in reducing the toxicity of AC to organisms and is the major reasons for the poor absorption of AC in vivo.