Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes.
ABSTRACT 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.
Article: Transactivation of genes encoding for phase II enzymes and phase III transporters by phytochemical antioxidants.[show abstract] [hide abstract]
ABSTRACT: The induction of phase II enzymes and phase III transporters contributes to the metabolism, detoxification of xenobiotics, antioxidant capacity, redox homeostasis and cell viability. Transactivation of the genes that encode for phase II enzymes and phase III transporters is coordinatively regulated by activating transcription factors in response to external stimuli. Comprehensive studies indicate that antioxidant phytochemicals promote the induction of phase II enzymes and/or phase III transporters through various signaling pathways, including phosphoinositide 3-kinase, protein kinase C, and mitogen-activated protein kinases. This paper focuses on the molecular mechanisms and signaling pathways responsible for the transactivation of genes encoding for these proteins, as orchestrated by a series of transcription factors and related signaling components.Molecules 01/2010; 15(9):6332-48. · 2.39 Impact Factor