title: Enteric excretion of baicalein, a flavone of Scutellariae Radix, via glucuronidation in rat: involvement of multidrug resistance-associated protein 2.
abstract: OBJECTIVE
  Baicalin (BG) and its aglycone, baicalein (B), are strong antioxidants and have various pharmacological actions. The purpose of this study was to evaluate efflux of BG from rat intestinal mucosal cell following glucuronidation of B absorbed after oral administration of B.
  
  
  METHODS
  The absorption and excretion of BG and B were evaluated in rats using the in situ jejunal loop technique and in vitro jejunal everted sac experiments. BG and B levels were determined by high-performance liquid chromatography with electro-chemical detection to ensure selectivity and high sensitivity.
  
  
  RESULTS
  A large amount (30.4% recovery) of BG, but no B, was detected in the intestinal lumens of germ-free rats 4 h after oral administration of B (12.1 mg/kg), in comparison with a substantial recovery (55.1%) of unabsorbed BG 4 h after its administration. During the in situ rat jejunal loop absorption experiment, B disappeared rapidly, and 8% of the lost B was excreted into the loop as BG 20 min after infusing 0.1 mM B. In an in vitro absorption experiment using everted rat jejunal sac, BG also appeared outside the sac, accompanied by the disappearance of B from the outer (mucosal) side. However, very little of B was transferred to the inner (serosal) side of the sac, and only a trace of BG was detected inside the sac. Thus, in both the loop and the everted sac systems, the efflux of BG from the mucosal surface was saturated with the concentration of B added. Moreover, the efflux rate of BG in the everted jejunal sac from Eisai hyperbilirubinemic rat (EHBR) was significantly lower by 56.4% than that from Sprague-Dawley rat.
  
  
  CONCLUSIONS
  These results indicate that, in rat, a large proportion of any B absorbed is retained, transformed into BG within the intestinal mucosal cells, and coordinately excreted through multidrug resistance-associated protein 2 (MRP2) into the intestinal lumen.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. ta0113@ms.toyama-mpu.ac.jp
authors.forename: Teruaki
authors.initials: T
authors.lastname: Akao
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sakashita
authors.forename: Masato
authors.initials: M
authors.lastname: Hanada
authors.forename: Hirozo
authors.initials: H
authors.lastname: Goto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Terasawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics*; D044950:Flavanones / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D031363:Scutellaria / Q000737:chemistry*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D044950:Flavanones; D020719:Glucuronides; C006680:baicalein; C095122:multidrug resistance protein 3