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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。
Flavonoids are a class of polyphenols widely found in nature. They have many pharmacological effects such as cardiovascular disease, anti-oxidation and anti-inflammatory. Studies have shown that the first pass caused by liver and intestine metabolism is an important factor limiting its clinical application. This review summarizes the research progress of the metabolism of flavonoids in order to provide reference for the metabolism research of flavonoids and the development of new drugs. In recent years, the literature is analyzed, summarized and summarized, respectively, according to in vivo method, in vitro and in vivo method introduced flavonoids metabolism research methods of progress and application prospects. The in vivo method mainly introduced the zebrafish model, humanized animal model and gene knockout animal model. The rat unilateral intestinal perfusion model was summarized in vitro. The Caco-2 cell model was mainly introduced in vitro, Incubation of body digestive tract content, microsomal gut, hepatocyte in vitro incubation and gene recombinant metabolic enzymes. In recent years, the continuous development of instruments and instruments such as LC-MS-MS and microdialysis has greatly enhanced the sensitivity and specificity of drug analysis methods and played an important role in the determination of trace drug concentration. In addition, some new models of biological and metabolic models such as zebrafish models, microbial population humanized animal models, knockout animal models and humanized liver chimerism mouse models provide new insights into the metabolism of flavonoids Ideas. At present, the research on the metabolism of flavonoids is developing rapidly. Various metabolic models and methods are bound to speed up the pace of research in this field with their own unique advantages and further promote the development and clinical application of new flavonoids.