Kreander Kari, Galkin Anna, Vuorela Satu, Tammela Päivi, Laitinen Leena, Heinonen Marina, Vuorela Pia
Drug Discovery and Development Technology Center, Faculty of Pharmacy, University of Helsinki, Finland.
J Pharm Pharmacol. 2006 Nov;58(11):1545-52. doi: 10.1211/jpp.58.11.0016.
This study investigated the mutagenic, anti-mutagenic and cytotoxic effects of acetone extract of raspberry, Rubus idaeus L. (v. Ottawa) Rosaceae, and the isolated and characterized ellagitannin and anthocyanin fractions thereof, suitable for food applications. The studied raspberry extract and fractions did not show any mutagenic effects determined in the miniaturized Ames test and were not cytotoxic to Caco-2 cells at the used concentrations. However, the anti-mutagenic properties were changed (i.e. decreased mutagenicity of 2-nitrofluorene in strain TA98, and slightly increased mutagenicity of 2-aminoanthracene in strain TA100) with metabolic activation. Further, their influence on the permeability of co-administered common drugs (ketoprofen, paracetamol, metoprolol and verapamil) across Caco-2 monolayers was evaluated. The apical-to-basolateral permeability of highly permeable verapamil was mostly affected (decreased) during co-administration of the raspberry extract or the ellagitannin fraction. Ketoprofen permeability was decreased by the ellagitannin fraction. Consumption of food rich in phytochemicals, as demonstrated here with chemically characterized raspberry extract and fractions, with well-absorbing drugs would seem to affect the permeability of some of these drugs depending on the components. Thus their effects on the absorption of drugs in-vivo cannot be excluded.
本研究调查了蔷薇科悬钩子属植物覆盆子(Rubus idaeus L.,品种渥太华)丙酮提取物及其分离鉴定的鞣花单宁和花色苷组分的诱变、抗诱变和细胞毒性作用,这些组分适用于食品应用。在所使用的浓度下,所研究的覆盆子提取物和组分在小型化艾姆斯试验中未显示出任何诱变作用,对Caco-2细胞也无细胞毒性。然而,在代谢活化作用下,其抗诱变特性发生了变化(即菌株TA98中2-硝基芴的诱变性降低,菌株TA100中2-氨基蒽的诱变性略有增加)。此外,还评估了它们对共同给药的常用药物(酮洛芬、对乙酰氨基酚、美托洛尔和维拉帕米)跨Caco-2单层细胞通透性的影响。在共同给药覆盆子提取物或鞣花单宁组分期间,高渗透性维拉帕米的顶侧至基底侧通透性受到的影响最大(降低)。酮洛芬的通透性因鞣花单宁组分而降低。正如这里用化学表征的覆盆子提取物和组分所证明的,食用富含植物化学物质的食物与吸收良好的药物一起,似乎会根据成分影响其中一些药物的通透性。因此,不能排除它们对体内药物吸收的影响。