title: Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells.
abstract: The human intracellular enzyme AKR1B1 belongs to the aldo-keto reductase superfamily. The AKR1B1-catalyzed reduction of aldehydes is part of the intracellular inflammatory pathway leading to the activation of NF-κB and the expression of pro-inflammatory genes. The present study is aimed at determining the inhibition of AKR1B1 brought about by an extract of artichoke leaves (bracts), and the effects of this extract and three participating compounds on the expression of AKR1B1, COX-2, and MMP-2 proteins in THP-1 cells. It seeks to identify the ability of the test substances to modulate the lipopolysaccharide (LPS)-induced activation of NF-κB in cells and the intracellular oxidant effect of test substances after incubation with LPS. Low concentrations of the extract inhibit the enzyme AKR1B1. After stimulation by LPS, the extract attenuated the activity of NF-κB in THP-1 cells, but no changes in the expression of AKR1B1 were recorded. The extract diminished the expression of the inflammation-related enzymes COX-2 and MMP-2, probably by inhibiting the activity of NF-κB. The extract significantly diminished the intracellular reactive oxygen species after a brief LPS incubation, which may also have reduced intracellular inflammation. The diminished activity of NF-κB in the cells could be linked to the inhibition of the activity of AKR1B1. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SR-83232, Bratislava, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Miláčková
authors.affiliation: Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SR-83232, Bratislava, Slovakia.
authors.forename: Kristína
authors.initials: K
authors.lastname: Kapustová
authors.affiliation: Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SR-83232, Bratislava, Slovakia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Mučaji
authors.affiliation: Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, CZ-61242, Brno, Czech Republic.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0003-0975-1671
authors.initials: J
authors.lastname: Hošek
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D031943:Cynara scolymus / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D010936:Plant Extracts; C498143:RELA protein, human; D051996:Transcription Factor RelA; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2
keywords: Cynara cardunculus; aldose reductase; antioxidant; inflammation