李莹;陈思颖;巩仔鹏;康宁芳;吴耽;唐娟;李月婷;潘洁;黄勇;郑林;兰燕宇;李勇军;王永林;
LI Ying;CHEN Si-ying;GONG Zi-peng;KANG Ning-fang;WU Dan;TANG Juan;LI Yue-ting;PAN Jie;HUANG Yong;ZHENG Lin;LAN Yan-yu;LI Yong-jun;WANG Yong-lin;Provincial Key Laboratory of Pharmaceutics in Guizhou, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine, School of Pharmacy, Guizhou Medical University;

• 1:贵州医科大学药学院贵州省药物制剂重点实验室省部共建药用植物功效与利用国家重点实验室民族药与中药开发应用教育部工程研究中心

摘要(Abstract)：

考察红禾麻提取物在正常与类风湿性关节炎病理状态下大鼠体内的肠吸收特性差异,采用大鼠离体外翻肠囊模型,以红禾麻提取物5.0 g·L~(-1)为吸收浓度,通过UPLC-MS/MS检测肠吸收液样品中新绿原酸、绿原酸、隐绿原酸、芦丁、山柰酚-3-O-芸香糖苷、木犀草苷、槲皮苷、异槲皮苷8种指标成分的含量,计算其累积吸收量(Q)和吸收速率常数(K_a),比较正常大鼠和类风湿性关节炎大鼠肠吸收液中红禾麻提取物各成分的吸收特征。结果表明,红禾麻提取物中8种指标成分均可吸收进入肠囊且成线性吸收,各成分的累积吸收量-时间曲线均为上升趋势,未呈饱和现象,其相关回归系数(R~2)均大于0.92,符合零级吸收速率过程,推测各成分可能的吸收方式为被动扩散。正常状态下各成分以回肠吸收最好(除绿原酸外),病理状态下以十二指肠吸收最好,且8种成分在类风湿性关节炎大鼠各肠段的总体吸收优于正常大鼠,推测类风湿性关节炎可能会改变药物吸收的特定部位。实验表明类风湿性关节炎会改变红禾麻提取物的肠吸收,其作用机制有待进一步的深入研究。
This work aimed to investigate the intestinal absorption characteristics of Laportea bulbifera extract in normal and rheumatoid arthritis model rats. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, galuteolin, quercetin and isoquercetin in intestinal absorption solution samples were detected by UPLC-MS/MS with 5.0 g·L~(-1) as the absorption concentration. The cumulative absorption(Q) and absorption rate constant(K_a) were calculated, and the absorption characteristics of different components of L. bulbifera in intestinal absorption solution of normal rats and rheumatoid arthritis rats were compared. The results showed that all the eight index components in the extract of L. bulbifera could be absorbed into the intestinal capsule, the cumulative absorption-time curve of each component showed an upward trend without saturation, and the correlation regression coefficient(R~2) was greater than 0.92, which is consistent with the zero-order absorption rate process. It was speculated that the possible absorption mode of each component was passive diffusion. In normal condition, the absorption of ileum was the best(except chlorogenic acid), and in pathological condition, duodenum was the best. The total absorption of 8 components in each intestinal segment of RA rats was better than that of normal rats, which speculated that rheumatoid arthritis may change the specific site of drug absorption. The experimental results showed that rheumatoid arthritis could change the intestinal absorption of the extract of L. bulbifera, and its mechanism needs further study.

关键词(KeyWords)： 红禾麻提取物;离体外翻肠囊模型;类风湿性关节炎大鼠;吸收
Laportea bulbifera extract;everted gut sac model;rheumatoid arthritis rats;absorption

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81560693,U1812403);; 贵州省民族药药效物质基础研究科技创新人才团队项目(黔科合平台人才[2016]5613);; 贵阳市科研创新团队项目(筑科合同[2017]30-29号);; 中央引导地方科技专项项目(黔科中引地[2018]4006);; 贵州省科技厅人才团队项目(黔科合平台人才[2016]5613/5677)

作者(Author): 李莹;陈思颖;巩仔鹏;康宁芳;吴耽;唐娟;李月婷;潘洁;黄勇;郑林;兰燕宇;李勇军;王永林;
LI Ying;CHEN Si-ying;GONG Zi-peng;KANG Ning-fang;WU Dan;TANG Juan;LI Yue-ting;PAN Jie;HUANG Yong;ZHENG Lin;LAN Yan-yu;LI Yong-jun;WANG Yong-lin;Provincial Key Laboratory of Pharmaceutics in Guizhou, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine, School of Pharmacy, Guizhou Medical University;

Email:

DOI:

参考文献(References)：

• [1] 池里群,周彬,高文远,等.治疗类风湿性关节炎常用药物的研究进展[J].中国中药杂志,2014,39(15):2851.
• [2] 贵州省药品监督管理局.贵州省中药材、民族药材质量标准[S].贵阳:贵州科技出版社,2003:187.
• [3] 唐娟,吴耽,陈思颖,等.基于UPLC-ESI-Q-TOF-MS的红禾麻提取物化学成分分析[J].中国实验方剂学杂志,2018,24(24):67.
• [4] 章平衡,刘健,纵瑞凯,等.佐剂性关节炎大鼠血小板活化与FAK/Calpain信号通路紊乱有关[J].中国免疫学杂志,2019,3(3):263.
• [5] 缪成贵,时维静,魏伟,等.王枣子总黄酮影响佐剂性关节炎大鼠病理的分子机制研究[J].中国中药杂志,2017,42(17):3411.
• [6] 缪成贵,周国梁,秦梅颂,等.白头翁皂苷对佐剂性关节炎大鼠FZD8表达的影响[J].中国中药杂志,2015,40(20):4063.
• [7] 巩仔鹏,李梅,侯靖宇,等.外翻肠囊法研究羊耳菊提取物在大鼠肠内的吸收[J].中国中药杂志,2018,43(3):609.
• [8] 朱晶晶,王智民,龚慕辛,等.基于肠吸收的质量评价指标选择的方法和原则[J].中国中药杂志,2011,36(6):659.
• [9] 刘跃,唐丽,曹旭,等.荭草提取物的肠外翻吸收研究[J].中国中药杂志,2014,39(11):2121.
• [10] 刘艺,程梅梅,董健健,等.外翻肠囊法研究肝豆汤醇提物主要成分的肠吸收特征[J].中国中药杂志,2017,42(13):2571.
• [11] Cressman A,Petrovic V,Piquette M.Inflammation-mediated changes in drug transporter expression/activity:implications for therapeutic drug response[J].Expert Rev Clin Pharmacol,2012,5(1):68.
• [12] Velusami C C,Richard E J,Bethapudi B.Polar extract of Curcuma longa protects cartilage homeostasis:possible mechanism of action[J].Inflammopharmacology,2018,26(5):1233.
• [13] Gul A,Kunwar B,Mazhar M,et al.Rutin and rutin-conjugated gold nanoparticles ameliorate collagen-induced arthritis in rats through inhibition of NF-κB and iNOS activation[J].Int Immunopharmacol,2018,59:310.
• [14] Kwak S,Lee C,Kim J,et al.Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-B ligand-induced nuclear factor of activated T cells c1 expression[J].Biol Pharm Bull,2013,36(11):1779.
• [15] Chauhan P,Satti N,Sharma P,et al.Differential effects of chlorogenic acid on various immunological parameters relevant to rheumatoid arthritis[J].Phytother Res,2011,26(8):1156.
• [16] 许晓林,柳蔚,李世刚,等.黄酮类化合物治疗类风湿性关节炎作用机制的研究进展[J].中药材,2013,36(8):1367.
• [17] 陈胤睿,徐文芬,马敏龙,等.红禾麻的研究进展[J].中国实验方剂学杂志,2019,25(18):214.