Zhang Li, Lin Ge, Zuo Zhong
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, PRC.
Life Sci. 2006 May 8;78(24):2772-80. doi: 10.1016/j.lfs.2005.10.038. Epub 2005 Dec 22.
Extensive intestinal glucuronidation has been previously reported in both human and animals after oral administration of naturally occurred flavonoids. The present study aims to investigate the relationship between human intestinal glucuronidation activity and the position of hydroxyl substitution on flavonoids. Seven commercially available mono-hydroxyflavones (HF), namely 3-, 5-, 6-, 7-, 2'-, 3'- and 4'-mono-hydroxyflavones, were chosen as model compounds. Glucuronidation activity of the selected seven HFs was investigated by incubating each HF at various concentrations with human jejunum S9 at 37 degrees C for 10 min. The generated glucuronides were identified by HPLC/MS and quantified by HPLC/UV. Metabolic kinetics parameters including Km and Vmax of each HF were determined. The results demonstrated that the glucuronidation activity of 6- and 3'-mono-hydroxyflavones was much greater than that of 3-, 4'-, 7- and 2'-HF with 5-HF to be the lowest. The findings imply that nucleophilicity and stereo-conformation of OH substituents are crucial for the intestinal glucuronidation of flavonoids.
先前已有报道称，人类和动物口服天然存在的黄酮类化合物后，肠道会发生广泛的葡萄糖醛酸化反应。本研究旨在探讨人类肠道葡萄糖醛酸化活性与黄酮类化合物上羟基取代位置之间的关系。选取了七种市售的单羟基黄酮（HF），即3 -、5 -、6 -、7 -、2' -、3' -和4' -单羟基黄酮作为模型化合物。通过将每种HF在不同浓度下与人类空肠S9在37℃孵育10分钟，研究了所选七种HF的葡萄糖醛酸化活性。通过HPLC/MS鉴定生成的葡萄糖醛酸苷，并通过HPLC/UV进行定量。测定了每种HF的代谢动力学参数，包括Km和Vmax。结果表明，6 -和3' -单羟基黄酮的葡萄糖醛酸化活性远高于3 -、4' -、7 -和2' - HF，其中5 - HF的活性最低。这些发现表明，OH取代基的亲核性和立体构象对于黄酮类化合物的肠道葡萄糖醛酸化至关重要。
