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.

Artichoke leaf extract, as AKR1B1 inhibitor, decreases sorbitol level in the rat eye lenses under high glucose conditions ex vivo

“…In conclusion, the present study extends our previous work on biological activities of artichoke leaf extract (Miláčková et al, ) revealing antioxidant activity in cultured C2C12 cells exposed to high glucose. In addition, the extract effectively inhibited accumulation of sorbitol in the rat eye lenses exposed to high glucose ex vivo.…”

“…The artichoke leaves are well known for their beneficial therapeutic effects in enhancing lipid metabolism, choleresis, and hepatic functions. In several studies, the extracts from artichoke leaves showed also decreasing activities of glucose level and beneficial effect on lipid metabolism of diabetic rats (Hosseini et al, ; Magied et al, ; Salem et al, ) as well as effective AKR1B1 and RL‐AKR inhibitions (Miláčková et al, ). Human AKR1B1 (and rat equivalent RL‐AKR) is the first enzyme of the polyol pathway that reduces glucose to sorbitol more intensively under diabetic conditions.…”

“…Our previous study reported on biological activities of artichoke leaf extract (Miláčková, Kapustová, Mučaji, & Hošek, ). The extract effectively inhibited isolated human aldose reductase AKR1B1 (IC 50 = 5.12 ± 0.11 μg/ml) and its rat equivalent rat lens aldose reductase (RL‐AKR; IC 50 = 3.06 ± 0.08 μg/ml) and effectively reduced NF‐κB activity during LPS incubation in human leukemic monocytes.…”

The antioxidant activity of artichoke (Cynara scolymus): A systematic review and meta‐analysis of animal studies

“…It is hypothesized that the antioxidant activity of artichoke might be related to following compounds: (a) polyphenolics (caffeoylquinic acids and flavonoids) and (b) Sesquiterpenes (Ben Salem & Affes, ; Brown & Rice‐Evans, ; Gebhardt, ; Miccadei et al, ; Miláčková et al, ; Perez‐Garcia et al, ; Rahimuddin et al, ; Takei et al, ). 1.…”

“…Polyphenolic compounds: (a) Caffeoylquinic acids: The chemical structure of caffeoylquinic acids is composed of one or two caffeic acid moieties and one quinic acid molecule. It is reported that cynarin (1,3‐O‐dicaffeoylquinic acid) and chlorogenic acid (5‐O‐caffeoylquinic acid), the most important caffeoylquinic derivatives in artichoke, would be partly responsible for antioxidant activity of artichoke (Gebhardt & Fausel, ; Miccadei et al, ; Miláčková et al, ; Pandino, Lombardo, Mauromicale, & Williamson, ; Perez‐Garcia et al, ). Recently, the antioxidant activity of chloregenic acid and cynarin was shown using various in vito antioxidant assays (Sato et al, ; Topal et al, ).…”