Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, National Research University-Khon Kaen University, Khon Kaen, 40002, Thailand.
J Appl Toxicol. 2012 Dec;32(12):994-1001. doi: 10.1002/jat.2740. Epub 2012 Apr 13.
The effects of six Thai fruits, namely banana, guava, mangosteen, pineapple, ripe mango and ripe papaya, on cytochrome P450 (P450) activities were investigated. The median inhibitory concentrations (IC(50) ) of each of the fruit juices on CYP1A1, CYP1A2, CYP2E1 and CYP3A11 activities were determined. Pineapple juice showed the strongest inhibitory effect against all the evaluated P450 isozyme activities in mouse hepatic microsomes, followed by mangosteen, guava, ripe mango, ripe papaya and banana. The study was further performed in male ICR mice given pineapple juice intragastrically at doses of 10, 20 and 40 mg kg(-1) per day for 7 or 28 days. In a concentration-dependent fashion, the pineapple juice raised ethoxyresorufin O-deethylase, aniline hydroxylase and erythromycin N-demethylase activities, which are marker enzymatic reactions responsible for CYP1A1, CYP2E1 and CYP3A11, respectively. The effect of pineapple juice on the expression of CYP1A1, CYP2E1 and CYP3A11 mRNAs corresponded to their enzymatic activities. However, the pineapple juice significantly decreased methoxyresorufin O-demethylase activity. These observations supported that the six Thai fruits were a feasible cause of food-drug interaction or adverse drug effects owing to their potential to modify several essential P450 activities. Individuals consuming large quantities of pineapple for long periods of time should be cautioned of these potential adverse effects.
六种泰国水果（香蕉、番石榴、山竹、菠萝、成熟芒果和成熟木瓜）对细胞色素 P450（CYP）活性的影响。测定了每种果汁对 CYP1A1、CYP1A2、CYP2E1 和 CYP3A11 活性的半数抑制浓度（IC50）。菠萝汁对所有评估的 CYP 同工酶活性均表现出最强的抑制作用，其次是山竹、番石榴、成熟芒果、成熟木瓜和香蕉。进一步在雄性 ICR 小鼠中进行了研究，这些小鼠经灌胃给予菠萝汁，剂量分别为每天 10、20 和 40 mg/kg，持续 7 或 28 天。菠萝汁以浓度依赖的方式升高了乙氧基香豆素 O-脱乙基酶、苯胺羟化酶和红霉素 N-脱甲基酶的活性，这是分别负责 CYP1A1、CYP2E1 和 CYP3A11 的标记酶反应。菠萝汁对 CYP1A1、CYP2E1 和 CYP3A11 mRNA 表达的影响与它们的酶活性相对应。然而，菠萝汁显著降低了甲氧基香豆素 O-脱甲基酶的活性。这些观察结果表明，六种泰国水果可能因其能够修饰几种重要的 CYP 活性而成为食物-药物相互作用或不良药物反应的可行原因。长期大量食用菠萝的个人应注意这些潜在的不良反应。
