Takanaga H, Ohnishi A, Matsuo H, Sawada Y
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Biol Pharm Bull. 1998 Oct;21(10):1062-6. doi: 10.1248/bpb.21.1062.
We investigated the effect of components in grapefruit juice (GFJ) on the transport of vinblastine, a substrate of P-glycoprotein (P-gp), across Caco-2 cells. The apical to basolateral flux of [3H]vinblastine was increased in the presence of GFJ extracts. The steady-state uptake of [3H]vinblastine from the apical side was significantly increased in the presence of GFJ in a dose-dependent manner within the range of 2.5 to 50% (v/v) of GFJ. Although naringin and naringenin reduced apical efflux of [3H]vinblastine at the concentration present in GFJ and increased steady-state uptake from the apical side to 124 and 240%, respectively, the observed effect of naringin was not enough to account for the effect of GFJ and naringenin is not naturally present in GFJ. To investigate the effective components in GFJ, we examined the inhibitory effect of several organic solvent extracts of GFJ on the transport of [3H]vinblastine in Caco-2 cells. Organic solvent extracts of GFJ enhanced the apical to basolateral transcellular transport and inhibited the apical efflux. The permeability coefficient of apical to basolateral transport of [3H]vinblastine increased in the order of the ethyl acetate>diethyl ether>methylene chloride extracts of GFJ. Since the extracted amount of naringenin by ethyl acetate was less than that with the other organic solvents, the primary inhibitor in GFJ is suggested to be different from this flavonoid. The present study demonstrated the existence of inhibitory components in GFJ for the P-gp function in Caco-2 cells, which are distinct from known components such as naringin or naringenin.
我们研究了葡萄柚汁（GFJ）中的成分对长春碱（一种P-糖蛋白（P-gp）底物）跨Caco-2细胞转运的影响。在GFJ提取物存在的情况下，[3H]长春碱从顶侧向基底侧的通量增加。在2.5%至50%（v/v）的GFJ范围内，GFJ存在时，[3H]长春碱从顶侧的稳态摄取以剂量依赖性方式显著增加。尽管柚皮苷和柚皮素在GFJ中的浓度下降低了[3H]长春碱的顶侧流出，并分别将顶侧的稳态摄取增加到124%和240%，但观察到的柚皮苷的作用不足以解释GFJ的作用，且柚皮素在GFJ中并非天然存在。为了研究GFJ中的有效成分，我们检测了GFJ的几种有机溶剂提取物对[3H]长春碱在Caco-2细胞中转运的抑制作用。GFJ的有机溶剂提取物增强了从顶侧向基底侧的跨细胞转运，并抑制了顶侧流出。[3H]长春碱从顶侧向基底侧转运的渗透系数按GFJ的乙酸乙酯提取物>二乙醚提取物>二氯甲烷提取物的顺序增加。由于乙酸乙酯提取的柚皮素量少于其他有机溶剂，因此推测GFJ中的主要抑制剂不同于这种类黄酮。本研究证明了GFJ中存在对Caco-2细胞中P-gp功能有抑制作用的成分，这些成分与柚皮苷或柚皮素等已知成分不同。
