金荞麦提取物主要活性成份在溃疡性结肠炎模型小鼠体内的组织分布  

Tissue distribution of main active components of Fagopyrum cymosum extracts in mice with ulcerative colitis

作　　者：葛飞[1] 祁明明[2] 刘丽娜[3] 严晶[3] 康安[4] 朱时林 季瑜[1] 田祖成 代海峰[1] 葛乃建[5] 

机构地区：[1]海安县中医院消化科,江苏省南通市226600 [2]南京中医药大学基础医学院,江苏省南京市210023 [3]南京中医药大学第一临床医学院,江苏省南京市210023 [4]南京中医药大学药学院,江苏省南京市210023 [5]第二军医大学东方肝胆外科医院微创介入中心,上海市200438

出　　处：《世界华人消化杂志》2017年第35期3123-3132,共10页World Chinese Journal of Digestology

基　　金：国家自然科学基金青年科学基金资助项目;Nos.81503536;81603578;江苏省自然科学基金青年科学基金资助项目;No.BK20151008;江苏省中医药局科技项目;No.YB2017066;江苏省高校自然科学研究面上资助项目;No.15KJB360008~~

摘　　要：目的研究金荞麦(fagopyrumcymosum,FAG)主要提取物中活性成分在硫酸葡聚糖(dextran sulfate sodium,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)小鼠模型体内组织分布特征.方法建立同时测定小鼠组织样品中FAG提取物中的4种活性成分,即儿茶素、表儿茶素、原花青素B_1及原花青素B_2的LC-MS/MS分析方法,考察该方法的专属性、线性、最低定量限、准确度和精密度、基质效应、回收率和稳定性.采用饮用3%DSS水7 d的方法建立UC小鼠模型,应用2.28 g/kg的FAG提取物给于正常及UC小鼠,于不同时间点取正常及UC小鼠的血浆、结肠、空肠、肝脏,用于后续的分析检测.结果方法学考察结果表明,该方法符合生物样品分析的要求,可用于测定生物样品中儿茶素、表儿茶素、原花青素B_1和原花青素B_2的浓度.FAG活性成份儿茶素、原花青素B_1和原花青素B_2在UC小鼠中的血浆暴露程度均有所增加,但不具显著性差异(P>0.05).组织分布结果表明其主要活性成分在UC小鼠的空肠、结肠组织及肝脏组织中的浓度比正常组要高.如表儿茶素在UC小鼠给药4 h后的结肠组织中(5.77μg/g±0.59μg/g)浓度显著大于正常小鼠(4.44μg/g±0.32μg/g)的结肠组织分布(P=0.0014).结论在UC病理状态下,FAG活性成分在肠道的高浓度分布,可以有效地保证其效应的发挥.AIM To investigate the tissue distribution of the main active components of Fagopyrum cymosum（FAG） extracts in dextran sulfate sodium（DSS） induced colitis mice.METHODS LC-MS/MS analytical method was developed to simultaneously determine catechin, epicatechin, procyanidin B1, and procyanidin B2, four main components of FAG extracts, in different mouse biological samples. The method was then validated by specificity, linearity, lower limit of quantification（LLOQ）, precision, accuracy, matrix effect, recovery, and stability tests. Ulcerative colitis was then induced in mice by administering 3% DSS in drinking water for 7 d. The plasma, liver, jejunum, and colon samples from normal mice or ulcerative colitis mice were collected to analyze the distribution of the main active components of FAG extracts in mice after oral administration of FAG extracts（2.24 g/kg）. RESULTS The initial method validation indicated that the LCMS/MS method could be used for determining the concentrations of catechin, epicatechin, procyanidins B_1, and procyanidins B_2 in mouse biological samples. The plasma exposures of catechin, epicatechin, procyanidins B_1, and procyanidins B_2 were increased in the DSS induced colitismice compared with normal mice, but there was no significant difference（P〈0.05）. However, in the tissue distribution study, we found that the concentrations of the main components of FAG in different tissue samples were significantly increased when compared with the normal mice. Taking epicatechin as an example, the concentration of epicatechin in the colitis tissue was significantly increased from 4.44 μg/g ± 0.32 μg/g to 5.77 μg/g ± 0.59 μg/g（P = 0.0014）.CONCLUSION Increased systemic exposures of main active components of FAG in ulcerative colitis may be beneficial for the therapeutic effects of FAG on ulcerative colitis.

关 键 词：金荞麦 硫酸葡聚糖 溃疡性结肠炎 药代动力学 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]