title: The effects of notoginsenoside R₁ on the intestinal absorption of geniposide by the everted rat gut sac model.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Chinese Medicine, Beijing University of Chinese Medicine, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing 100102, PR China.
authors.forename: Sa
authors.initials: S
authors.lastname: Chula
authors.forename: Lv
authors.initials: L
authors.lastname: Hang
authors.forename: Ba
authors.initials: B
authors.lastname: Yinying
authors.forename: Sun
authors.initials: S
authors.lastname: Jianning
authors.forename: Renbing
authors.initials: R
authors.lastname: Shi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D036145:Ginsenosides / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D039823:Iridoids / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D036145:Ginsenosides; D039823:Iridoids; C007835:geniposide; D020112:Rhodamine 123; D014700:Verapamil; C072936:notoginsenoside R1