INVESTIGATION OF OVERINTAKE AND DRUG INTERACTION OF FUNCTIONAL FOOD COMPONENTS

在世界范围内，功能性食品已被用于多种疾病的预防。虽然功能性食品的健康益处值得注意，但其风险评估也不容忽视。在本研究中，我研究了膳食多酚的基本生物利用度以及食品成分与药物的相互作用。蔓越莓富含多酚类物质，包括花青素和原花青素，已被证明对人体健康有多种有益作用，包括预防尿路感染。蔓越莓多酚的生物利用度鲜为人知。采用LC-ESI-MS/MS对人摄入蔓越莓汁后尿液中的44种代谢物进行了鉴定。其中，o -甲基化原花青素a -2是一种新的代谢物。水解单宁包括鞣花单宁存在于浆果和坚果等食物中。鞣花单宁的多种生物活性，包括抗氧化、抗病毒和抗肿瘤活性，已被注意和报道。我研究了大鼠摄入鞣花单宁、天竺葵苷后尿液和肠道微生物代谢物的特征。采用柱层析和/或制备高效液相色谱法分离大鼠尿液，得到7种代谢物M1-M7。根据光谱数据和化学证据确定了这些代谢物的结构。除Ml外，这些化合物均首次被鉴定为鞣花单宁代谢产物。此外，在尿中的四种主要代谢物（M1-M4）中，M2显示出与完整的天竺葵苷和相关多酚相当的抗氧化活性。食品成分和药物之间的相互作用最近成为人们关注的焦点。这种相互作用通常是由于抑制或诱导代谢酶细胞色素P450 （CYP）而发生的。众所周知，与葡萄柚汁同时摄入可通过抑制CYP3A4的激活来增加人体内钙拮抗剂的浓度。蔓越莓汁传统上被用来预防尿路感染。然而，据报道，食用蔓越莓汁后华法林的潜在影响。这种相互作用的原因主要是未知的。研究蔓越莓提取物、成分及相关多酚类物质对CYP2C9和CYP3A4的抑制作用。因此，肠道微生物代谢物如酚酸没有表现出影响。香豆素类化合物、黄酮类化合物和黄酮醇类化合物有较强的抑菌活性。这些结果提示，部分膳食多酚可能具有抑制药物代谢的潜力，需要进一步研究以明确其临床意义。少

Functional foods have been used as prevention of several diseases in worldwide. Although its health benefit is noteworthy, the risk assessment of functional foods cannot be disregarded. In this study, I investigated the basic bioavailability of dietary polyphenol and the interaction between food components and medicine.Cranberry, which is rich in polyphenols including anthocyanins and proanthocyanidins, has been demonstrated to have various effects beneficial to human health including prevention of urinary tract infection. The bioavailability of cranberry polyphenols is little known. Forty-four metabolites in human urine after ingestion of cranberry juice were identified by using LC-ESI-MS/MS. Among metabolites, O-methylated proanthocyanidin A-2 were characterized as a new metabolite.Hydrolyzable tannins including ellagitannins occur in foods such as berries and nuts. Various biological activities, including antioxidant, antiviral and antitumor activities, have been noted and reported … More for ellagitannins, but the absorption and metabolism of purified ellagitannins are poorly understood. I investigated the characterization of urinary and intestinal microbial metabolites in rats after the ingestion of ellagitannin, geraniin. Rat urine sample was separated by column chromatography and/or preparative HPLC, to give seven metabolites, M1-M7. The structures of these metabolites were determined basis on spectroscopic data and chemical evidence. These compounds except for Ml were characterized as ellagitannin metabolites for the first time. Furthermore, among four major metabolites (M1-M4) in urine, M2 showed an antioxidant activity comparable to intact geraniin and related polyphenols.Interactions between food components and drugs have recently come into focus of interest. The interactions often occur as a result of inhibiting or inducing of the metabolic enzymes, cytochrome P450 (CYP). It is well known that concomitant intake with grapefruit juice increases the concentration of calcium antagonists in human by suppression of CYP3A4 activation. Cranberry juice has been traditionally used for the prevention of urinary tract infection. However, potentiated effects of warfarin following consumption of cranberry juice have been reported. The reasons for the interaction are mainly unknown. I study the inhibitory effects of cranberry extracts and ingredients, and related polyphenols on CYP2C9 and CYP3A4. Consequently, the gut microbial metabolites such as phenolic acids showed no effect. A part of compounds of coumarins, fiavones and flavonols exhibited a strong inhibitory activity.These results suggested that a part of dietary polyphenols might have the potential to inhibit the metabolism of drugs, so that further study should be investigated to clarify the clinical relevance. Less