In vitro investigation of permeability and metabolism of licoricidin.

Aim Licoricidin has multiple pharmacological activities. The present study was designed to investigate the permeability and pharmacokinetic behavior of licoricidin using in vitro models. MATERIAL AND METHODS First, human liver microsomes and recombinant human supersomes were used to investigate the interactions between metabolic enzymes and licoricidin. In addition, rat, minipig, rabbit, dog, monkey, and human liver microsomes were used to determine metabolic differences among species. The parallel artificial membrane permeability assay (PAMPA) was used to explore licoricidin permeability behavior. KEY FINDINGS At 100 μM, licoricidin strongly inhibited CYP2C9, CYP2C19, CYP3A4, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17. Licoricidin metabolism exhibited considerable differences among species; dog, pig, and rat liver microsomes showed higher metabolic capacity than the other species. Seven licoricidin metabolites were identified by liquid chromatography-tandem mass spectrometry, and hydration and hydroxylation were the major metabolic pathways. The PAMPA permeability of licoricidin was moderate at both pH 4.0 and 7.4. SIGNIFICANCE The present study will support further pharmacological or toxicological research on licoricidin.

• Publication year

  2019

• Venue

  Life Science

• Publication date

  2019-10-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.lfs.2019.116770PMID 31421085
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug-drug interaction.

  2018cited by this paper
• Cyanobacterial production of plant essential oils

  2018cited by this paper
• Downregulation of the CpSRP43 gene expression confers a truncated light-harvesting antenna (TLA) and enhances biomass and leaf-to-stem ratio in Nicotiana tabacum canopies

  2018cited by this paper
• Biotechnology of cyanobacterial isoprene production

  2018cited by this paper
• Predicting a Drug's Membrane Permeability: A Computational Model Validated With in Vitro Permeability Assay Data.

  2017cited by this paper
• The inhibitory effects of β-caryophyllene, β-caryophyllene oxide and α-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver in vitro.

  2017cited by this paper
• Assessment of the inhibition risk of shikonin on cytochrome P450 via cocktail inhibition assay.

  2017cited by this paper
• Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

  2017cited by this paper
• On the use of the experimentally determined enzyme inhibition constant as a measure of absolute binding affinity

  2017cited by this paper
• Licoricidin inhibits the growth of SW480 human colorectal adenocarcinoma cells in vitro and in vivo by inducing cycle arrest, apoptosis and autophagy

  2017cited by this paper
• Licoricidin, an isoflavonoid isolated from Glycyrrhiza uralensis Fisher, prevents UVA‐induced photoaging of human dermal fibroblasts

  2017cited by this paper
• Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays.

  2017cited by this paper
• Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review

  2016cited by this paper
• Comparison of the in vitro metabolism of psoralidin among different species and characterization of its inhibitory effect against UDP- glucuronosyltransferase (UGT) or cytochrome p450 (CYP450) enzymes.

  2016cited by this paper
• The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes

  2016cited by this paper
• Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report

  2016cited by this paper
• Metabolites identification of bioactive licorice compounds in rats.

  2015cited by this paper
• Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and Centella asiatica in Human Liver Microsomes

  2015cited by this paper
• Inhibition of in vitro metabolism of testosterone in human, dog and horse liver microsomes to investigate species differences.

  2015cited by this paper
• Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements

  2015cited by this paper
• Evaluation of Inhibitory Effects of Caffeic acid and Quercetin on Human Liver Cytochrome P450 Activities

  2014cited by this paper
• In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity.

  2014cited by this paper
• Cytochrome P450 mRNA Expression in the Rodent Brain: Species-, Sex-, and Region-Dependent Differences

  2014cited by this paper
• Metabolites identification of glycycoumarin, a major bioactive coumarin from licorice in rats.

  2014cited by this paper
• Drug-Drug Interactions Potential of Icariin and Its Intestinal Metabolites via Inhibition of Intestinal UDP-Glucuronosyltransferases

  2012cited by this paper
• Assessment of drug-drug interactions caused by metabolism-dependent cytochrome P450 inhibition.

  2012cited by this paper
• Molecular docking and enzyme kinetic studies of dihydrotanshinone on metabolism of a model CYP2D6 probe substrate in human liver microsomes.

  2012cited by this paper
• Reduction of bacterial volatile sulfur compound production by licoricidin and licorisoflavan A from licorice

  2012cited by this paper
• Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A: potential therapeutic approach for periodontitis.

  2011cited by this paper
• Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification.

  2011cited by this paper
• Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method.

  2011cited by this paper
• Analysis of CYP3A4-HIV-1 protease drugs interactions by computational methods for Highly Active Antiretroviral Therapy in HIV/AIDS.

  2010cited by this paper
• Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells.

  2010cited by this paper
• Identification of the major chemical constituents and their metabolites in rat plasma and various organs after oral administration of effective Erxian Decoction (EXD) fraction by liquid chromatography-mass spectrometry.

  2009cited by this paper
• C-7 configuration as one of determinants in taxanes metabolism by human cytochrome P450 enzymes

  2009cited by this paper
• Mechanistic analysis of pH-dependent solubility and trans-membrane permeability of amphoteric compounds: application to sildenafil.

  2008cited by this paper
• Permeation characteristics of a hydrophilic basic compound across a bio-mimetic artificial membrane.

  2004cited by this paper
• Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

  2003cited by this paper
• The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9.

  2002cited by this paper
• Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans.

  2001cited by this paper
• Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes.

  1998cited by this paper
• Measurement of protein using bicinchoninic acid.

  1985cited by this paper

• Licoricidin Ameliorates Renal Function via Controlling Stress and Inflammation in Experimental Diabetic Nephropathy Animal Model

  2025cites this paper
• Herb-Drug Interactions and Their Impact on Pharmacokinetics: an Update.

  2023cites this paper
• Metabolism of gartanin in liver microsomes and its modulating effects on cytochrome P450s

  2022cites this paper
• Species Difference in the Metabolism of Mulberrin in Vitro and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes.

  2022cites this paper
• Licoricidin improves neurological dysfunction after traumatic brain injury in mice via regulating FoxO3/Wnt/β-catenin pathway

  2020cites this paper
• An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone

  2020cites this paper
• Interspecies metabolic diversity of artocarpin in vitro mammalian liver microsomes

  2019cites this paper