Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability.
Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability.
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DOI：
10.1158/1940-6207.capr-12-0281
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Steward WP
中科院分区：
文献类型：
--
作者：
Irving GR;Howells LM;Sale S;Kralj-Hans I;Atkin WS;Clark SK;Britton RG;Jones DJ;Scott EN;Berry DP;Hemingway D;Miller AS;Brown K;Gescher AJ;Steward WP
姜黄素是姜黄的主要成分，被怀疑具有癌症化学预防特性。已经报道了药代动力学和药效学参数，但很少有数据描述方法是否适合用于结肠活检标本中的姜黄素检测。关于每日姜黄素长期给药的可接受性的信息不可用。这对于实施化学预防策略至关重要。本研究旨在量化接受结肠直肠内窥镜检查或手术切除的患者的结肠直肠粘膜中姜黄素的水平，并获得有关每日姜黄素的可接受性和依从性的信息。姜黄素C3复合物（2.35克）给予患者，每天一次，持续14天前，内镜活检或结肠切除术。监测安全性和耐受性。通过UPLC-UV进行血浆、尿液和结肠粘膜中姜黄素类化合物的分析，并通过串联LC-MS/MS进行表征。开始服用姜黄素的26名患者中有24名完成了疗程。6例患者报告了轻度胃肠道不良事件。在所有23名活检参与者的9/24份血浆样本、24/24份尿液样本和结肠粘膜中均可检测到类姜黄素。母体姜黄素的平均组织水平为48.4 μg/g（127.8 nmol/g）。在29/35例活检中可检测到主要结合物姜黄素葡糖苷酸。高水平的局部姜黄素持续在粘膜长达40小时后给药。16名参与者（67%）表示，如果证明姜黄素有益，他们将长期服用姜黄素。总之，从结肠粘膜中回收了抗肿瘤活性水平的姜黄素。这里使用的方案似乎是安全的，患者支持在长期试验中使用。
Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3-complex (2.35 g) was administered to patients once daily for 14 days prior to endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine and colonic mucosa was performed by UPLC-UV with characterisation by tandem LC-MS/MS. Twenty four out of 26 patients commencing curcumin completed the course. Six patients reported mild gastro-intestinal adverse events. Curcuminoids were detectable in 9/24 plasma samples, 24/24 urine samples and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 μg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate, curcumin glucuronide, was detectable in 29/35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 h post-administration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here appears safe, and patients support its use in long-term trials.