【作者】 李婷；

【导师】 刘继华；

【作者基本信息】 吉林大学 ， 药物分析学， 2019， 硕士

【摘要】 人参具有治疗糖尿病、抗炎、抗癌、增强免疫和治疗心血管疾病等功效,是临床上的大补药。据文献报道人参的主要活性成分是人参皂苷,目前对人参总皂苷的体内代谢研究较少。本文将6年生晒园参用水进行煎煮,灌胃大鼠进行体内代谢研究,分析人参水煎液和人参总皂苷水溶液分别给药后,人参皂苷类成分药代动力学和体内代谢产物的异同。研究结果将为人参相关药物的研发奠定理论基础。1、口服人参水煎液和人参总皂苷水溶液的入血代谢成分研究本章节采用超高效液相串联四级杆飞行时间质谱（UPLC-Q/TOF-MS）结合UNIFI科学信息学系统分析小鼠口服人参水煎液和人参总皂苷水溶液入血代谢产物的异同点。根据实验数据得出结论:（1）代谢产物:口服人参水煎液后,代谢产物中人参二醇型皂苷衍生物居多,且以人参二醇型皂苷元加2个糖代谢物为主。人参三醇型皂苷代谢物较二醇型少,代谢产物多为皂苷元加1个糖和2个糖代谢物。（2）代谢途径:两者在代谢途径上无明显区别。唯一不同的是,口服人参水煎液后,检测到甘氨酸结合的代谢产物,而口服人参总皂苷水溶液后的代谢物中未检测到甘氨酸代谢物。2、人参总皂苷加不同比例人参多糖口服给药后的入血代谢成分研究本章节将人参总皂苷加人参多糖（1:0.5）,（1:2）和（1:4）三个比例灌胃小白鼠,采用UPLC-Q/TOF-MS结合UNIFI科学信息学系统分析给药后体内代谢产物的异同点。实验数据表明:人参总皂苷加不同比例人参多糖对人参总皂苷体内代谢的影响作用是:（1）代谢产物:随着人参总皂苷加人参多糖比例的增加,代谢产物中人参二醇型皂苷衍生物和奥克梯隆型皂苷衍生物增多。（2）代谢途径:人参总皂苷加不同比例的人参多糖给药后,代谢途径无明显区别,说明人参多糖的加入对人参总皂苷的生物转化反应无明显影响。3、大鼠口服人参水煎液和人参总皂苷水溶液后的人参皂苷Rb₁、Rc和Rd的血药动力学研究实验采用UPLC-Q/TOF-MS结合DAS 3.0软件研究大鼠灌胃人参水煎液和人参总皂苷水溶液后人参皂苷单体Rb₁、Rc和Rd的药时曲线,得出结论:相比人参总皂苷组入血的Rb₁,人参水煎液组AUC和C_max分别提高了3.2倍和3.7倍,表明人参水煎液与人参总皂苷水溶液给药相比,Rb₁体内吸收得到增强,生物利用度增大。大鼠口服人参水煎液后入血Rc的AUC和C_max值小于人参总皂苷组,而且T_max没有明显改变,揭示了大鼠口服人参水煎液后,人参皂苷Rc的体内转化增强,T_1/2数值较大,说明消除缓慢,MRT数值没有明显变化。大鼠口服人参水煎液后,入血原型药Rd达峰时间与Rb₁相同均是8h,Cmax和AUC均小于Rb₁和Rc,T_1/2和MRT与Rb₁相同。更多还原

【Abstract】 Ginseng was widely used as a nutritious drug in clinic for their therapeutic effects on cardiovascular disorders,diabetes,nerve disease,inflammation,cancer etc.According to reports in literature,the main active components of ginseng were ginsenosides.Nevertheless,few investigations were available about metabolites and pharmacokinetics（PK）of total ginsenosides.Accordingly,to explore the PK behaviors and metabolites of ginsenosides after orally administered ginseng decoction（GD）and total ginsenosides（TG）,the six-year-old ginseng were boiled to get ginseng decoction,powders of TG were dissolved in water to get TG aqueous,which were both administered to mice and rats.The results of this study will set up theoretical and experimental basis for the new drug development of panax ginseng.1.Structural identification of metabolites of GD and TGUltra-performance liquid chromatograph tandem time-of-flight mass spectrometry（UPLC-Q/TOF-MS）combined with UNIFI data processing system was used to analyze the metabolites of ginsenosides after orally administered GD and TG.The results showed that most of the metabolites are propanaxadiol derivatives after oral GD,and the main metabolites are propanaxadiol combined 2 sugars;the metabolites of protopanaxtriol type were less than those of protopanaxdiol type,and commoly combined 1 or 2 sugar in the molecular structure.There was no significant difference of metabolic pathway between the two administrations.The only difference was that glycine-binding metabolites were detected after oral administration of GD,but not detected after oral administration of TG.2.Structural identification of metabolites of TG plus different proportions of polysaccharidesThe metabolites of ginsenosides after oral administration of different ratio of ginseng polysaccharides and TG were determined by the method of UPLC-Q/TOF-MS coupled with UNIFI software,which the ratios were 1:0.5,1:2,1:4respectively.Based on the results of the experiments,it was concluded that propanaxadiol type of ginsenoside metabolites and ocotillol metabolites increased with the ratio of ginsenosides to polysaccharides rising.There was no significant difference of metabolic pathway after oral administration of TG with different ratio of polysaccharides,indicating that ginseng polysaccharides had no significant effect on the original biotransformation of ginsenoside in vivo.3.The PK behaviors of ginsenoside Rb1,Rc,Rd after oral GD and TGPK behaviors of Rb₁,Rc and Rd after oral administration of GD and TG were studied.Compared the data of Rb₁ after oral administration of TG,the values of AUC and C_maxax were 3.2,and 3.7 times after oral administration of GD,explaining that the absorption of Rb₁ was enhanced,the bioavailability of Rb₁ was higher.The AUC and C_maxax of Rc after oral GD were less than oral administration of TG,but T_maxax did not change,suggesting that there was enhanced transformation of Rc after oral administration of GD compared of TG.In addition,T_1/2 of Rc after oral GD was much longer than TG,but MRT was not changed significantly.After oral administration of GD,the peak time of Rd reached 8 hours,Cmax and AUC were less than Rb₁ and Rc,and T_1/2 and MRT were the same as Rb₁.更多还原