Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes.
Liquiritigenin (LQ), an active component of licorice, has an inhibitory effect on LPS-induced inhibitory nitric oxide synthase expression. This study investigated the effects of LQ on choleresis, the expression of hepatic transporters and phase-II enzymes, and fulminant hepatitis. The choleretic effect and the pharmacokinetics of LQ and its glucuronides were monitored in rats. After intravenous administration of LQ, the total area under the plasma concentration-time curve of glucuronyl metabolites was greater than that of LQ in plasma, which accompanied elevations in bile flow rate and biliary excretion of bile acid, glutathione, and bilirubin. The expressions of hepatocellular transporters and phase-II enzymes were assessed by immunoblots, real-time PCR, and immunohistochemistry. In the livers of rats treated with LQ, the protein and mRNA levels of multidrug resistance protein 2 and bile salt export pump were increased in the liver, which was verified by their increased localizations in canalicular membrane. In addition, LQ treatment enhanced the expression levels of major hepatic phase-II enzymes. Consistent with these results, LQ treatments attenuated galactosamine/LPS-induced hepatitis in rats, as supported by decreases in the plasma alanine aminotransferase, liver necrosis, and plasma TNF-alpha. These results demonstrate that LQ has a choleretic effect and the ability to induce transporters and phase-II enzymes in the liver, which may be associated with a hepatoprotective effect against galactosamine/LPS. Our findings may provide insight into understanding the action of LQ and its therapeutic use for liver disease.
Kim
Young Woo
YW
College of Pharmacy, Seoul National University, Seoul, Korea.
Kang
Hee Eun
HE
Lee
Myung Gull
MG
Hwang
Se Jin
SJ
Kim
Sang Chan
SC
Lee
Chang Ho
CH
Kim
Sang Geon
SG
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000378:metabolism; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism; D044950:Flavanones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005688:Galactosamine; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D050217:Metabolic Detoxication, Phase II; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation; D000097202:ATP-Binding Cassette Sub-Family B Member 4; D000099148:UGT1A1 Enzyme
D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D002756:Cholagogues and Choleretics; D004798:Enzymes; D004851:Epoxide Hydrolases; D044950:Flavanones; D005688:Galactosamine; D020719:Glucuronides; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D006419:Heme Oxygenase (Decyclizing); D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C490548:Abcb11 protein, rat; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C491523:Hmox1 protein, rat; C119995:glutathione S-transferase alpha; C083152:liquiritigenin