Mechanism of oral absorption of panaxnotoginseng saponins
- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 6
- DOI:
- 10.3321/j.issn:0513-4870.2006.06.004
- Key Word:
- 三七总皂苷;Caco-2细胞;生物利用度;人参皂苷Rb1;人参皂苷Rg1
Abstract： 目的研究三七总皂苷(PNS)的口服吸收机制.方法采用Caco-2细胞和动物等模型研究PNS中人参皂苷Rb1(Rb1)和人参皂苷Rg1(Rg1)的胃肠道内稳定性、肠道黏膜吸收机制及吸收过程中胃、肠及肝对药物的影响.结果 Rb1和Rg1在胃液酸性环境下易被破坏,而在近中性环境内基本保持稳定.Rb1和Rg1在大肠内容物中易降解,尤以Rb1降解较为明显;二者在小肠内容物中则相对稳定.Rb1和Rg1在Caco-2细胞层的摄取受温度的影响,而pH的变化及环孢菌素A的加入对二者摄取均无显著性影响.在实验考察的浓度范围内,细胞内Rb1(或Rg1)的摄取量随Rb1(或Rg1)的浓度的增加而呈线性增加,Rb1(或Rg1)单体与总皂苷中的Rb1(或Rg1)在Caco-2细胞模型中的吸收特性无明显差异.而Rg1的细胞摄取量[(1.07±0.16)μg·mg-1(protein)](C0=1 mg·mL-1)相对Rb1[(0.77±0.03)μg·mg-1(protein)](C0=1 mg·mL-1)较高.Caco-2细胞转运实验表明,Rb1和Rg1单体的转运透过系数(Pspp)分别为(5.9±1.0)×10-8cm·s-1和(2.59±0.17)×10-7 cm·s-1(C0=1 mg·mL-1),二者转运都不受环孢菌素A影响.PNS溶液灌胃、十二指肠及门静脉给药后测得Rb1大鼠绝对生物利用度分别为0.71%,2.75%和65.77%;Rg1分别为3.29%,6.60%和50.56%.结论三七总皂苷(包括Rb1和Rg1)的肠道吸收机制为单纯被动扩散,吸收过程不受细胞膜内P-gp和MRP外排载体的调控,PNS中其他成分对Rb1或Rg1的吸收特性无明显影响.胃液的酸性环境、大肠菌丛产生的酶及肝脏的首过作用均对其口服吸收产生影响,而肠道黏膜的透过性低是其口服吸收差的主要影响因素.
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