TY - JOUR
T1 - Enteric excretion of baicalein, a flavone of Scutellariae Radix, via glucuronidation in rat
T2 - Involvement of multidrug resistance-associated protein 2
AU - Akao, Teruaki
AU - Sakashita, Yoko
AU - Hanada, Masato
AU - Goto, Hirozo
AU - Shimada, Yutaka
AU - Terasawa, Katsutoshi
N1 - Funding Information:
We thank the Laboratory Animal Research Center of Toyama Medical & Pharmaceutical University for maintaining the rats. This study was supported by a Grant-in Aid for Scientific Research and a Grant-in Aid for the 21st Century COE Program from Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2004
Y1 - 2004
N2 - Purpose. 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 resis- tance-associated protein 2 (MRP2) into the intestinal lumen.
AB - Purpose. 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 resis- tance-associated protein 2 (MRP2) into the intestinal lumen.
KW - Baicalein
KW - Baicalin
KW - Glucuronidation
KW - Intestinal excretion
KW - MRP2
UR - http://www.scopus.com/inward/record.url?scp=21644436299&partnerID=8YFLogxK
U2 - 10.1023/B:PHAM.0000048205.02478.b5
DO - 10.1023/B:PHAM.0000048205.02478.b5
M3 - 学術論文
C2 - 15587936
AN - SCOPUS:21644436299
SN - 0724-8741
VL - 21
SP - 2120
EP - 2126
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 11
ER -