In the previous study, the artichoke leaf extract showed effective inhibition of AKR1B1, the first enzyme of polyol pathway, which reduces high level of glucose to osmotically active sorbitol, important for development of chronic diabetic complications. In the present study, the effect of artichoke leaf extract and of several participating phenols (caffeic acid, chlorogenic acid, quinic acid, and luteolin) was tested on sorbitol level in rat lenses exposed to high glucose ex vivo, on cytotoxicity as well as on oxidative stress in C2C12 muscle cell line induced by high glucose in vitro. The concentration of sorbitol was determined by enzymatic analysis, the cytotoxicity was provided by WST-1 test and intracellular content of reactive oxygen species was determined by fluorescence of 2'-7'-dichlorofluorescein probe. The extract and the compounds tested showed significant protection against toxic effects of high concentration of glucose in both models. On balance, the artichoke leaf extract thus represents a prospective preventive agent of development of chronic diabetic complications, probably due to phenols content, concerning preclinical and clinical studies.
- Klíčová slova
- Cynara cardunculus, aldo-keto reductases, chronic diabetic complications, glucose toxicity, oxidative stress, polyol pathway,
- MeSH
- aldehydreduktasa antagonisté a inhibitory MeSH
- Cynara scolymus chemie MeSH
- glukosa farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- listy rostlin chemie MeSH
- myši MeSH
- oční čočka účinky léků metabolismus MeSH
- orgánové kultury - kultivační techniky MeSH
- oxidační stres účinky léků MeSH
- reaktivní formy kyslíku farmakologie MeSH
- rostlinné extrakty farmakologie MeSH
- sorbitol metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Akr1b1 protein, rat MeSH Prohlížeč
- aldehydreduktasa MeSH
- glukosa MeSH
- inhibitory enzymů MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty MeSH
- sorbitol MeSH
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.
- Klíčová slova
- Cynara cardunculus, aldose reductase, antioxidant, inflammation,
- MeSH
- aldehydreduktasa antagonisté a inhibitory genetika metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- Cynara scolymus chemie MeSH
- down regulace účinky léků MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- leukemie genetika metabolismus patologie MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- listy rostlin chemie MeSH
- matrixová metaloproteinasa 2 genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- rostlinné extrakty farmakologie MeSH
- signální transdukce účinky léků genetika MeSH
- transkripční faktor RelA antagonisté a inhibitory metabolismus MeSH
- zánět chemicky indukované genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AKR1B1 protein, human MeSH Prohlížeč
- aldehydreduktasa MeSH
- cyklooxygenasa 2 MeSH
- lipopolysacharidy MeSH
- matrixová metaloproteinasa 2 MeSH
- RELA protein, human MeSH Prohlížeč
- rostlinné extrakty MeSH
- transkripční faktor RelA MeSH
