School of Chinese Medicine, Beijing University of Chinese Medicine, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing 100102, PR China.
J Ethnopharmacol. 2012 Jun 26;142(1):136-43. doi: 10.1016/j.jep.2012.04.027. Epub 2012 Apr 26.
Geniposide is derived from Gardenia jasminoides Ellis (Rubiaceae). Its anti-inflammatory, antithrombotic effects as well as its preventive effect against ischemic stroke have been reported. Radix notoginseng (Chinese name tienchi or sanqi) is the dried root of Panax notoginseng (Burk.) F.H. Chen, an herb noted for its promotion of blood circulation, blood stasis removal and pain alleviation, and has been widely utilized for the prevention and treatment of microcirculatory disturbances in China and other Asian countries for many years. Notoginsenoside R₁ is an effective and structurally representative bioactive constituent of R. notoginseng. In our preliminary study, notoginsenoside R₁ was able significantly to improve the bioavailability of geniposide in beagle dogs, but the underlying mechanisms remain unknown.
The present study aimed to investigate the intestinal kinetic absorptive characteristics of geniposide as well as the absorptive behavior influenced by the co-administration of notoginsenoside R₁ using an in vitro everted rat gut sac model.
The results showed good linear correlation between the geniposide absorption in sac contents and the incubation time from 0 to 120 min. The concentration dependence showed a non-linear correlation between the geniposide absorption and the concentrations 0.356-1.424 mg/mL, the absorption was saturated about 1.424 mg/mL. Notoginsenoside R₁ at 0.1 and 0.2mg/mL concentrations was able significantly to enhance the absorption of geniposide (1.424 mg/mL) by 1.7- and 1.4-fold. Moreover, verapamil, a well-known P-glycoprotein inhibitor, was able significantly to elevate the absorption of geniposide 2.4-fold. Notoginsenoside R₁ influenced geniposide's absorption in a way similar to that of a P-glycoprotein inhibitor.
In conclusion, notoginsenoside R₁ significantly enhances the intestinal absorption of geniposide. As for the mechanism underlying the improvement of geniposide's bioavailability, it is proposed that notoginsenoside R₁ was able to decrease the efflux transport of geniposide by P-glycoproteins.
栀子苷来源于栀子（茜草科）。据报道，它具有抗炎、抗血栓作用以及预防缺血性中风的作用。三七是人参的干根，以促进血液循环、祛瘀止痛而闻名，多年来在中国和其他亚洲国家被广泛用于预防和治疗微循环障碍。三七皂苷 R₁是三七的一种有效且结构代表性的生物活性成分。在我们的初步研究中，三七皂苷 R₁能够显著提高栀子苷在比格犬体内的生物利用度，但具体机制尚不清楚。
本研究旨在使用体外翻肠囊模型研究栀子苷的肠动力吸收特征以及三七皂苷 R₁共同给药对其吸收行为的影响。
结果表明，囊内容物中栀子苷的吸收与 0 至 120 分钟的孵育时间之间呈良好的线性相关性。浓度依赖性表明，栀子苷的吸收与 0.356-1.424mg/mL 的浓度之间呈非线性关系，当浓度约为 1.424mg/mL 时吸收达到饱和。浓度为 0.1 和 0.2mg/mL 的三七皂苷 R₁能够分别显著将 1.424mg/mL 的栀子苷的吸收增强 1.7 倍和 1.4 倍。此外，维拉帕米是一种众所周知的 P-糖蛋白抑制剂，能够显著将栀子苷的吸收提高 2.4 倍。三七皂苷 R₁以类似于 P-糖蛋白抑制剂的方式影响栀子苷的吸收。
总之，三七皂苷 R₁显著增强了栀子苷的肠道吸收。至于提高栀子苷生物利用度的潜在机制，推测三七皂苷 R₁能够减少 P-糖蛋白对栀子苷的外排转运。
