苦参总生物碱及其单体在Caco-2细胞模型的吸收特征研究

目的 建立同时测定Caco-2细胞模型中苦参碱、氧化槐果碱和氧化苦参碱的HPLC方法,探讨苦参总生物碱在Caco-2细胞模型的吸收机制.方法 利用人源结肠腺癌细胞系Caco-2细胞单层模型,研究苦参碱、氧化槐果碱和氧化苦参碱由细胞绒毛膜面供给侧(AP)→基底外侧(BL)和BL→AP侧两个方向的转运过程；HPLC-UV法测定上述3个生物碱的量；计算转运参数和表观渗透系数(Papp).结果 苦参总碱给药后,苦参碱、氧化槐果碱和氧化苦参碱由AP→BL侧的Papp分别为(1.098±0.092)×10-5、(1.434±0.098)×10-5、(3.87±0.64)×10-6cm/s,由BL→AP侧的Papp分别为(1.104±0.098)×10-5、(1.034±0.079)×10-5、(2.75±0.33)×10-6 cm/s,与文献报道的单体化合物给药相比,氧化槐果碱和氧化苦参碱双向转运的Papp明显增大.苦参碱、氧化槐果碱和氧化苦参碱的表观渗透率值分别为1.01、0.72、0.71.结论 苦参总生物碱中苦参碱、氧化槐果碱和氧化苦参碱仍主要以被动吸收方式进入体内,但比各单体给药吸收更好.

Absorption characteristic of total alkaloids from Sophora flavescens and their monomers in Caco-2 cell model

Objective To establish an HPLC method for the simultaneous quantification of matrine (M),oxysophocarpine (OSP), and oxymatrine (OM), and to investigate the absorption mechanism of the total alkaloids from Sophora flavescens(TASF) in Caco-2 cell model. Methods By using Caco-2 cell monolayer model as an intestinal epithelial cell model, the transport processes of M, OSP, and OM from the apical (AP) side to the basolateral (BL) side or from BL side to AP side were studied. The contents of the three alkaloids were measured by HPLC-UV method. Transport parameters and apparent permeability coefficients (Papp) were then calculated. Results After TASF treatment, the Pappvalues of M, OSP, and OM were (1.098 ± 0.092) × 10?5, (1.434 ± 0.098) × 10?5,and (3.87 ± 0.64) × 10?6 cm/sfrom AP side to BL side, and (1.104 ± 0.098) × 10?5, (1.034 ± 0. 079) × 10?5, and (2.75 ± 0.33) × 10?6 cm/sfrom BL side to AP side, respectively. Compared with those ofmonomeric compound reported by literature, the Papp values of OSP and OM in bi-direction were increased obviously. The apparent permeability rates of M, OSP, and OM were 1.01, 0.72, and 0.71, respectively. Conclusion The M, OSP, and OM in TASF could still be absorbed across intestinal epithelial cells in passive transference forms, but could obtained the better absorption than in monomeric forms.