肠吸收屏障对栀子苷及其苷元京尼平的处置作用

Disposition of Geniposide and Genipin via Intestinal Absorption Barrier

目的研究肠吸收屏障对栀子苷及其苷元京尼平的处置作用,旨为其新制剂设计提供理论依据。方法采用肠道菌和肠道酶孵育法研究肠道环境对栀子苷的生物转化作用;应用大鼠在体肠灌流模型研究京尼平表观渗透性。结果肠道菌对栀子苷代谢活性为(1 098.3±519.2)μmol·h-1·g-1,栀子苷在肠道酶HBSS溶液中孵育4 h,浓度从20.00μmol·L-1下降至9.60μmol·L-1,而其代谢产物京尼平升至3.52μmol·L-1。京尼平在各肠段的有效渗透系数(P eff*)值在2.11±0.62~3.77±0.38,10 cm肠段吸收百分比(10 cm%ABS)在(48.52±9.59)%^(70.24±7.88)%,其中十二指肠对京尼平的吸收明显高于其他肠段(P<0.05)。胆汁中发现京尼平Ⅱ相代谢产物。结论肠道菌群及肠壁的酶均可以将栀子苷代谢为京尼平;京尼平肠道吸收较好;京尼平葡萄糖醛酸代谢产物可经过胆汁排泄。

OBJECTIVE To study the disposition of geniposide and genipin via intestinal absorption barrier. METHODS The biotransformation of geniposide was studied by incubating it with intestinal flora or intestinal enzymes. The intestinal absorption of genipin at duodenum, jejunum, ileum and colon was investigated using single-pass intestinal perfusion model. RESULTS The metabolism activity of intestinal flora for geniposide was （ 1 098.3 ± 519. 2） μmol · h^- 1 . g^-1. The concentration of geniposide reduced from 20. 00 to 9. 60 μmol · h^- 1 . g^-1 after 4 h of incubation with intestinal enzymes, while the concentration of the metabolite of geniposide, genipin, increased to 3.52 μmol · h^- 1 . g^-1. The effective permeability coefficients （Peff^＊） of ginipin at duodenum, jejunum, ileum, and colon were 3.77 ±0. 38, 3.00 ±0. 20, 2. 79 ±0. 16, and 2. 11 ±0. 62, respectively,and the absorption percentages at different intestinal segments of 10 cm long（ 10 em % ABS） were （70.24 ± 7.88 ） %, （56. 94 ± 4. 34） %, （53.44 ± 3.73 ） %, and （48.52 ± 9. 59 ） %, respectively. There were significant differences between duodenum and the other regions of intestine of rats （ P 〈 0. 05 ）. The phase Ⅱ metabolite of genipin was found in rat bile, and its UV absorption spectrum was in accordance with that of genipin hydrolyzed by β-glucuronidase. CONCLUSION Geniposide can be transformed to genipin in rat intestine. Genipin can be well absorbed in general intestinal tract without specific absorption site. The phase Ⅱ metabolite of genipin can be excreted to small intestine through bile.