【作者】 赵艳红；

【导师】 贾晓斌；

【作者基本信息】 江苏大学 ， 生药学， 2007， 硕士

【摘要】 本课题设计研究淫羊藿药材生晶及炮制品中淫羊藿苷、朝藿定A、朝藿定B、朝藿定C和宝藿苷Ⅰ几种单体化学成分及总黄酮提取物的吸收代谢行为，从有效成分吸收代谢的角度阐述淫羊藿的炮制机理。分离制备的淫羊藿苷(icariin，1)、淫羊藿次苷Ⅰ(icarisideⅠ，2)、3，5，7，4′-四羟基-8-异戊烯基黄酮-7-O-β-D-吡喃葡萄糖-3-O-B-D-吡喃葡萄糖苷(hexandraside E，3)、淫羊藿苷元(icaritin，4)、去甲基淫羊藿苷元(demethylicaritin，5)、宝藿苷Ⅰ(baohuosideⅠ，6)六种单体化合物为课题的顺利进行提供基础和必要条件。主成分的肠吸收代谢动力学研究考察了淫羊藿中黄酮类化合物的大鼠在体肠吸收特性和肠道菌代谢行为，分别比较分析了淫羊藿苷、朝藿定A、朝藿定B、朝藿定C和淫羊藿总黄酮的大鼠在体肠吸收及肠道菌代谢的差异。大鼠在体肠灌流实验结果表明，淫羊藿苷单体在大鼠各肠段的吸收与淫羊藿总黄酮中淫羊藿苷在大鼠各肠段的吸收特征相一致。淫羊藿苷在大鼠肠段不同部位的吸收存在差异，其中回肠和结肠肠段肠壁渗透系数显著低于十二指肠和空肠肠段。另外，在淫羊藿苷单体进行肠灌流时接收淫羊藿苷的肠灌流流出液和胆汁，在肠灌流流出液中能检测到宝藿苷Ⅰ；胆汁中能检测到宝藿苷Ⅰ但是小能检测到淫羊藿苷，由此可以推测淫羊藿苷在大鼠肠道被代谢为宝藿苷Ⅰ后再被吸收进入体内。将淫羊藿苷、朝藿定A、朝藿定B、朝藿定C与淫羊藿总黄酮提取物的肠吸收结果进行比较分析发现，淫羊藿总黄酮中淫羊藿苷经过大鼠肠段后代谢最为明显。离体大鼠肠道菌代谢实验结果显示出淫羊藿苷、朝藿定A、朝藿定B、朝藿定C在大鼠肠道菌作用下均能产生多种代谢产物。淫羊藿苷的大鼠整体肠内菌代谢研究结果显示出，大鼠灌服淫羊藿苷单体后其粪便、尿液和血清中均检测到宝藿苷Ⅰ的存在。课题组其他研究成员采用Caco-2细胞模型研究了这几种单体化合物的吸收代谢情况，实验结果显示出单糖苷(宝藿苷Ⅰ)的渗透系数比二糖苷(淫羊藿苷)高，而二糖苷(淫羊藿苷)比三糖苷(如朝藿定A、朝藿定B、朝藿定C等)的渗透系数高，说明淫羊藿中次级糖苷比多糖苷在大鼠肠道的渗透系数高，吸收比多糖苷好。加热温度和时间对淫羊藿药材中有效成分含量的影响结果显示，加热会改变淫羊藿药材中黄酮类物质的相对含量。在一定的加热温度和时间范围内，淫羊藿苷的含量增加最为明显，宝藿苷Ⅰ的含量也有一定增加，而朝藿定A、朝藿定B、朝藿定C的含量呈下降趋势。上述这些结论初步验证了假说：炮制会改变淫羊藿中黄酮类化学组分的配比，多糖苷(如朝藿定A、朝藿定B、朝藿定C等)含量降低而低级糖苷(如淫羊藿苷、宝藿苷Ⅰ等)含量增加，次级糖苷的渗透系数比多糖苷的渗透系数高，吸收比多糖苷好。由此可以得出结论：炮制可以提高淫羊藿中黄酮类化合物在体内的吸收。更多还原

【Abstract】 This project was designed to study the intestinal absorption and metabolism kineticsof main constituents including icariin, epimedin A, epimedin B, epimedin C,baohuosideⅠand total flavonoids in herba epimedii of crude and processing sample, andexplain the processing mechanisms of herba epimedii from the aspect of absorption andmetabolism kinetics of active components.We had prepared icariin（1）, icarisideⅠ（2）, Hexandraside E（3）, icaritin（4）,desmethylicariin（5）, baohuosideⅠ（6）, these compounds provide elementary andnecessary qualification to the study.The studies on intestinal absorption and metabolism kinetics of main constituentswas performed by using in situ perfused rat intestinal model and intestinal bacteriametabolism experiment, compared the difference of icariin, epimedin A, epimedin B,epimedin C, baohuosideⅠand total flavonoids in the aspect of intestinal absorption andmetabolism kinetics. The absorption characteristics and mechanism of active compoundsfor various intestinal segments in rats showed that icariin was metabolized quickly in theintestine. Some constituents of the total flavonoids showed metabolic transformation, andicariin showed obviously metabolism. Studies on the metabolism of flavonoid compoundsin Herba Epimedii by intestinal flora were described. Icariin、epimedin A、epimedin B andepimedin C were all metabolized quickly in vitro by rat intestinal flora, and icariin couldbe metabolized in vivo by rat intestinal flora. Some metabolites were observed in ratserum samples、urine samples and feces samples. We found that the main metabolite isbaohuosideⅠin both experiments of intestinal absorption and metabolism kinetics. Themethod used for metabolites analysis was HPLC and HPLC-MS. The results of Caco-2cell model showed that the permeability coefficient(P^*_eff) of baohuosideⅠwas higherthan icariin and the permeability coefficient(P^*_eff) of icariin was higher than epimedin A、epimedin B and epimedin C, so the absorption of baohuosideⅠwas best in all thesecompounds.Studies on the variation of active compounds in herba epimedii about the differenceof heating temperature and heating time, it could establish a basis to make a standard ofprocessing. The traditional processing method is to roast by adding quantitive meltedadept ovillus, and the leaves of the herb were heating in course of processing, but thestructure of these flavonoids was destroyed easily by light, heat and so on. To standard theprocess method, it is necessary to study the influence of active compounds in herba epimedii due to the temperature and time about heat.These conclusions authenticated previous hypothesis: processing would alter relativeratio of flavonoids in harba epimedii, the content of polycose glycoside was degrade, butthe content of deutero-polycose glycoside was increased. The permeability coefficient ofdeutero-polycose glycoside is higher than polycose glycoside, so the absorption ofpolycose glycoside is much better. And then, we draw a conclusion that processing canelevate the absorption of flavonoids in herba epimedii in vivo.更多还原