远志、厚朴配伍对其活性成分在大鼠肠段吸收的影响  

Active elements from Yuanzhi and Houpo,and their intestinal absorption due to the combined use

作　　者：黄立华[1] 王建[1] 吴明权[1] 朱璋佩 高天慧[1] 陆小华[1] 

机构地区：[1]成都中医药大学药学院,教育部重点实验室中药标准化实验室,四川成都611137

出　　处：《中成药》2015年第4期739-745,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(81173567)

摘　　要：目的研究远志和厚朴配伍对其活性成分细叶远志皂苷,远志口山酮Ⅲ,和厚朴酚,厚朴酚在大鼠不同肠段的吸收影响。方法采用在体单向肠灌流模型,用重量法校正灌流液体积,通过HPLC-DAD测定肠灌流液中的被测成分质量浓度,以及P-糖蛋白(P-gp)和多药耐药相关蛋白2(MRP2)抑制剂对吸收的影响。结果配伍组细叶远志皂苷在空肠、结肠的Ka、Papp值均显著低于远志组(P<0.05,P<0.01),远志口山酮Ⅲ在各肠段的Ka、Papp值与远志组比较均有减小趋势;配伍组和厚朴酚、厚朴酚的Ka、Papp值与厚朴组比较均有增大趋势。加入不同P-gp抑制剂盐酸维拉帕米后,各组中细叶远志皂苷、远志口山酮Ⅲ和厚朴酚的Ka值和中、高浓度组中厚朴酚的Ka值均显著高于空白组(P<0.05,P<0.01)。加入MRP2抑制剂吲哚美辛后,各组中细叶远志皂苷及中、高浓度组中远志口山酮Ⅲ的Ka、Papp值均极显著高于空白组(P<0.01),和厚朴酚与厚朴酚的Ka、Papp值均有高于空白组的趋势。结论厚朴能抑制远志中细叶远志皂苷、远志口山酮Ⅲ在空肠和结肠的吸收,但受P-gp和MRP2外排影响,提示两成分可能是P-gp和MRP2的底物;而远志能促进厚朴中和厚朴酚、厚朴酚的吸收,但均不是P-gp和MRP2的底物,远志和厚朴配伍不宜与P-gp和MRP2酶抑制剂同用。AIM To explore the intestinal absorption of tenuifolin,onjixanthone Ⅲ,honokiol,and magnolol by the combined use of Yuanzhi（ Polygalae Radix） and Houpo（ Magnoliae officinalis Cortex）. METHODS HPLC-DAD was applied to measureing the above mentioned active components contents in one-way intestinal perfusion model with corrected perfusate gravimetric method. Moreover,the influence to the absorption site,inhibitor,and the effect on permeability glycoprotein（ P-gp） and multidrug resistance-associated protein（ MRP2） by the combined use of Yuanzhi and Houpo were assessed. RESULTS Kaand Pappof tenuifolin on jejunum and colon in combination group was lower than that of Yuanzhi group（ P〈 0. 01,P〈 0. 05）. Kaand Pappof onjixanthoneⅢ in intestinal segments tended to decrease compared to Yuanzhi group. Kaand Pappof honokiol and magnolol in combination group performed differently compared to Houpo group. Kaof tenuifolin,onjixanthone Ⅲ,and honokiol in each group and Kaof magnolol in middle and high concentrations were significantly higher than these in the blank group（ P〈 0. 05,P〈 0. 01） adding of Verapamil. Kaand Pappof tenuifolin in groups and onjixanthone Ⅲ in middle and high concentration were significantly higher than these in the blank group（ P〈 0. 01） due to Indometacin,but Kaand Pappof honokiol and magnolol were found higher in the trial group. CONCLUSION Houpu can inhibit the absorption of tenuifolin and onjixanthone Ⅲ in jejunum and colon,given the efflux of P-gp and MRP2 and possibly the substrates of P-gp and MRP2. Whereas Yuanzhi can improve the absorption of honokiol and magnolol in jejunum and colon,but not because of the substrates of P-gp and MRP2. The combination of Yuanzhi and Houpo must avoid sharing with P-gp and MRP2 enzyme inhibitor.

关 键 词：远志 厚朴 配伍 肠吸收 在体单向肠灌流 细叶远志皂苷 远志口山酮Ⅲ 和厚朴酚 厚朴酚 P-糖蛋白 多药耐药相关蛋白2 

分 类 号：R969.1[医药卫生—药理学]