黄酮类化合物的代谢研究进展

黄酮类化合物是一类广泛存在于自然界中的多酚类化合物,具有治疗心血管疾病、抗氧化、抗炎等多种药理作用。研究表明肝肠引起的首过代谢是限制其临床应用的重要因素。本文综述了黄酮类化合物的代谢研究进展,以期为黄酮类药物的代谢研究及新药开发提供参考。对近几年的文献进行分析、归纳和总结,分别按照体内法、在体法和体外法介绍黄酮类化合物代谢研究方法的进展和应用前景。体内法中重点介绍了斑马鱼模型、菌群人源化动物模型和基因敲除动物模型;在体法总结了大鼠单向肠灌流模型;体外法中主要介绍了Caco-2细胞模型、离体消化道内容物温孵法、肝肠微粒体法、肝细胞体外温孵法和基因重组代谢酶法。近年来,LC-MS-MS、微透析技术等仪器和手段的不断发展大大提高了药物分析方法的灵敏度和专属性,在微量药物浓度测定方面发挥了重要作用。此外,一些新的模式生物和代谢模型如斑马鱼模型、菌群人源化动物模型、基因敲除动物模型和人源化肝脏嵌合体小鼠模型为黄酮类化合物的代谢研究提供了新的研究思路。目前黄酮类化合物的代谢研究发展迅速,各种代谢模型及方法必将以自身独特的优势加快人们对该领域的研究步伐,进一步推动黄酮类新药的开发及临床应用。

Research Progress on Metabolism of Flavonoids

Flavonoids are polyphenolic compounds that are ubiquitous in nature with extensive pharmacological activities, such as the treatment of cardiovascular diseases, antioxidant and anti-inflammatory. However, the clinical application of flavonoids was often limited by first-pass metabolism in the gut and the liver. This article reviews the studies on the metabolism of flavonoids in order to provide references for relative research and new drug development. The paper analyzed and summarized the literature in recent years, the in vivo, the in situ and the in vitro method were introduced. The in vivo method mainly included the zebrafish model, the flora humanized animal models and the gene knockout models. The in situ method mainly introduced the rat single-pass intestinal perfusion model. The in vitro method included the Caco-2 cell model, the gastrointestinal contents hatching method, the enterohepatic microsomal method and the genetic recombination metabolic enzyme method. In recent years, The continuous development of instruments and means such as the LC-MS-MS, the micro dialysis technology greatly improved the sensitivity and specificity of pharmaceutical analysis, which have played an important role in determination of trace drug concentration. Furthermore, Some new models, such as the zebrafish model, the flora humanized animal models, the gene knockout models and the humanized liver chimeric mouse model provided some new ideas for the metabolism of flavonoids. The study on the metabolism of flavonoid developed rapidly, Various metabolic models and methods is bounding to accelerate the pace of research in this field and promote the new drug development and clinical application.