竹节参总皂苷中10种活性成分在正常、肥胖大鼠体内药动学比较

Comparison of in vivo pharmacokinetics of ten active constituents from total saponins in Panax japonicus in normal and obese rats

目的比较竹节参总皂苷中人参皂苷Re、Rg1、Rf、Rb1、Rg2、Rd,竹节参皂苷Ⅴ、Ⅳ、Ⅳa,拟人参皂苷RT1在正常、肥胖大鼠体内药动学。方法大鼠随机分为正常组和肥胖组,灌胃给予总皂苷0.4%CMC-Na混悬液(0.8 g/kg),于0、0.08、0.25、0.5、0.75、1、1.5、2、4、6、8、12、24、48 h采血,UPLC-MS法测定各活性成分血药浓度,计算主要药动学参数。结果各活性成分C_(max)、AUC_(0~t)与其在总皂苷中的含量呈正相关。竹节参皂苷Ⅴ、Ⅳ、Ⅳa为体内主要暴露成分,t_(1/2)、MRT_(0~t)更长。与正常组比较,肥胖组各活性成分C_(max)(除人参皂苷Rg1)、AUC_(0~t)(除人参皂苷Re、Rg1和拟人参皂苷RT1)降低,t_(1/2)、MRT_(0~t)、T_(max)无明显变化。结论肥胖可影响竹节参总皂苷中部分活性成分的体内药动学,竹节参皂苷Ⅴ、Ⅳ、Ⅳa可能是竹节参总皂苷改善肥胖的关键组分。

AIM To compare the in vivo pharmacokinetics of ginsenosides Re,Rg1,Rf,Rb1,Rg2,Rd,chikusetsusaponins Ⅴ,Ⅳ,Ⅳa and pseudoginsenoside RT1 from total saponins in Panax japonicus C.A.Mey.in normal and obese rats.METHODS Rats were randomly assigned into normal groups and obese group and given intragastric administration of the 0.4%CMC-Na suspension of total saponins(0.8 g/kg),after which blood collection was performed at 0,0.08,0.25,0.5,0.75,1,1.5,2,4,6,8,12,24,48 h,UPLC-MS was adopted in the plasma concentration determination of various active constituents,and main pharmacokinetic parameters were calculated.RESULTS The C_(max)and AUC_(0-t)of various active constituents demonstrated positive correlations with their contents in total saponins.chikusetsusaponins Ⅴ,Ⅳ,Ⅳa were main exposed components,along with longer t_(1/2)and MRT_(0-t).Compared with the normal group,the obese group displayed decreased C_(max)(except for ginsenoside Rg1)and AUC_(0-t)(except for ginsenosides Re,Rg1 and pseudoginsenoside RT1)for various active constituents,while t_(1/2),MRT_(0-t)and Tmaxexhibited no obvious changes.CONCLUSION Obesity can affect the in vivo pharmacokinetics of some active constituents from total saponins in P.japonicus.chikusetsusaponins Ⅴ,Ⅳ,Ⅳa may be the key ingredients improving obesity from total saponins in P.japonicus.