人参多糖对人参皂苷Re体内代谢和体外转化的影响

Effects of Ginseng Polysaccharides on the Metabolism of Ginsenoside Re in vivo and Transformation of Ginsenoside Re in vitro

利用快速分离液相色谱-四极杆飞行时间质谱联用仪(RRLC/Q-TOF-MS)研究了人参多糖对肠道菌群转化人参皂苷Re的影响;考察了人参皂苷Re的代谢产物Rg1在口服人参多糖大鼠体内的药代动力学,并与正常大鼠体内Rg1的药代动力学参数进行了比较.结果表明,体外肠道菌群转化人参皂苷Re的主要转化产物有人参皂苷Rg1,Rh1,Rg2,F1和原人参三醇(Protopanaxatriol,PPT),分别归属于3条转化路径;正常情况下,肠道菌群转化人参皂苷Re 48 h时,除了终产物PPT的存在,中间产物Rg1,Rg2和F1仍可被检测到,而加入人参多糖后,只检测到终产物PPT.当口服给药Re后,代谢产物Rg1的达峰时间(tmax)、最大血浆浓度(cmax)和血浆药物浓度-时间曲线下面积(AUC)分别为(11.6±6.1) h,(80.1±44.0) ng/m L和(549.3±209.4) ng·h/m L;当给予人参多糖14 d后,口服给药Re,代谢产物Rg1的tmax,cmax和AUC分别为(8.2±5.4) h,(98.2±50.6) ng/m L和(691.9±231.2) ng·h/m L.研究结果表明,人参多糖能促进人参皂苷Re转化为人参皂苷Rg1,进而提高胃肠道对人参皂苷Rg1的吸收,并可能增强人参的药理作用.

To study the effect of ginseng polysaccharides on the absorption of ginsenoside Re metabolite into the blood and the transformation of ginsenoside Re by intestinal microflora in vitro,rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry(RRLC/Q-TOF-MS)was performed to investigate the biotransformation process of ginsenoside Re by intestinal microflora in media with and without ginseng polysaccharides,and the pharmacokinetics of the ginsenoside Re metabolite,ginsenoside Rg1,in rats with or without pretreatment with ginseng polysaccharides.For transformation of Re by rat intestinal microflora,five transformed products including ginsenoside Rg1,Rh1,Rg2,F1 and PPT,as well as three transformation pathways were identified.When the intestinal microbiota of rat feces was cultured in vitro,their ginsenoside Re biotransformation activities were significantly induced by ginseng polysaccharides.When ginsenoside Re was orally administered to rats,the peak time(t max),the maximum plasma concentration(c max)and area under the plasma drug concentration-time curve(AUC)for the main metabolite,ginsenoside Rg1,were(11.6±6.1)h,(80.1±44.0)ng/mL and(549.3±209.4)ng·h/mL,respectively.When ginsenoside Re was orally administered to rats fed ginseng polysaccharides,t max,c max and AUC for ginsenoside Rg1 were(8.2±5.4)h,(98.2±50.6)ng/mL and(691.9±231.2)ng·h/mL,respectively.The results show that ginseng polysaccharides may promote the metabolic conversion of ginsenoside Re to Rg1 and the subsequent absorption of Rg1 in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng.