配伍对芒果苷在INS-1细胞药代动力学的影响及其在细胞内的分布

Effects of compatibility on pharmacokineticsof mangiferin in INS-1 cells and its intracellular distribution

目的考察配伍黄柏对知母中芒果苷(mangiferin,MGF)在INS-1细胞药代动力学特征的影响,及芒果苷在正常和氧化损伤状态的INS-1细胞内的分布变化。方法以芒果苷单体、知母和知母-黄柏药对形式等剂量给药INS-1细胞,运用LC-MS/MS测定INS-1细胞中MGF的含量;设置正常组和模型组(140μmol·L^(-1 )H _(2)O _(2)处理INS-1细胞1 h),给药100μmol·L^(-1 ) MGF,分离线粒体、细胞核及胞质并检测其中的MGF。结果与单体给药相比,知母和药对给药后MGF在细胞内的浓度升高,药对组AUC_((0-t))明显高于单体组和知母组(P<0.01);INS-1细胞单次给药MGF 100μmol·L^(-1 )后,正常组MGF主要分布于细胞核,模型组MGF主要分布于胞质;与正常组相比,MGF在模型组的线粒体和胞质中C _(max)和AUC_((0-t))升高(P<0.01),细胞核中C _(max)和AUC_((0-t))明显降低(P<0.05)。结论配伍黄柏对知母有效成分芒果苷进入INS-1细胞具有促进作用;氧化损伤处理会改变MGF在INS-1细胞内的分布。

Aim To investigate the effect of compatibility of phellodendron amurense on the pharmacokinetics of mangiferin(MGF)in INS-1 cells,and the distribution of mangiferin in normal and oxidatively damaged INS-1 cells.Methods INS-1 cells were administered in equal doses of mangiferin,anemarrhena and anemarrhena-phellodendron herb pair.LC-MS/MS was used to determine the content of MGF in INS-1 cells.The normal and model groups(INS-1 cells were treated with 140μmol·L^(-1 ) H _(2)O _(2) for 1 h)were set up,and administered 100μmol·L^(-1 ) MGF,then the mitochondria,nuclei and cytosol of INS-1 cells were separated to detect the content of MGF.Results Compared with the mangiferin administration,the concentration of MGF in cells increased after the administration of anemarrhena and the herb pair,and the AUC_((0-t))of herb pair group was significantly higher than that of MGF group and anemarrhenae group(P<0.01).After 100μmol·L^(-1 ) MGF intervention in INS-1 cells,MGF was mainly distributed in nucleus of cells.However,in model group,it was mainly distributed in cytoplasm.Compared with normal group,the C _(max) and AUC_((0-t))in the mitochondria and cytoplasm of model group significantly increased(P<0.01),but the values in nucleus were significantly reduced(P<0.05).Conclusions Anemarrhena-phellodendron herb pair can promote the absorption of mangiferin in INS-1 cells.The oxidative damage treatment will change the distribution of MGF in INS-1 cells.