防风对痛泻要方活性成分在正常大鼠体内的药动学和组织分布的影响Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats
梁瑞峰,葛文静,魏征,张雪侠,崔伟锋,刘雪,李更生
LIANG Rui-feng,GE Wen-jing,WEI Zheng,ZHANG Xue-xia,CUI Wei-feng,LIU Xue,LI Geng-sheng
摘要(Abstract):
痛泻要方是治疗肝脾不和之痛泻的经典方剂,方中防风具有引经作用。该研究采用超高效液相色谱串联质谱(UPLC-MS/MS),以正负离子切换,多反应监测模式(MRM)同时测定大鼠灌胃不同配伍痛泻要方后血浆和组织中4种活性成分,比较不同配伍之间4种活性成分药动学和组织分布差异,探讨防风对痛泻要方主要成分的影响。研究发现,防风可提高芍药苷、橙皮苷的C_(max),AUC_(0-t),AUC_(0-∞),增加肝、脾、脑和小肠中白术内酯Ⅰ、芍药苷、橙皮苷的分布浓度,减少肺中白术内酯Ⅰ和没食子酸的分布;通过计算组织与血浆中的药物浓度比发现,防风可显著提高白术内酯Ⅰ、芍药苷、橙皮苷的脑/血浆比,降低白术内酯Ⅰ、芍药苷的肺/血浆比和芍药苷的脾/血浆比,推测防风可能通过增加痛泻要方有效成分的脑分布发挥引经作用。
Tongxie Yaofang( TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine( TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However,the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs,we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring( MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance C_(max),AUC_(0-t),and AUC_(0-∞) of paeoniflorin and hesperidin,and increase the distribution of atractylenolide-I,paeoniflorin and hesperidin in liver,spleen,brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolideI,paeoniflorin and hesperidin. Meanwhile,it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix,and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.
关键词(KeyWords):
防风;痛泻要方;药代动力学;组织分布;引经
Saposhnikoviae Radix;Tongxie Yaofang;pharmacokinetic;tissue distribution;meridian guiding
基金项目(Foundation): 河南省科技攻关计划项目(162102310373);; 河南省中医药科研专项(2016ZY2022);; 河南省省属科研机构预研专项基金(YY1603579)
作者(Author):
梁瑞峰,葛文静,魏征,张雪侠,崔伟锋,刘雪,李更生
LIANG Rui-feng,GE Wen-jing,WEI Zheng,ZHANG Xue-xia,CUI Wei-feng,LIU Xue,LI Geng-sheng
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- 防风
- 痛泻要方
- 药代动力学
- 组织分布
- 引经
Saposhnikoviae Radix - Tongxie Yaofang
- pharmacokinetic
- tissue distribution
- meridian guiding