5-lipoxygenase is a key enzyme in the synthesis of leukotrienes from arachidonic acid. The produced leukotrienes are involved in inflammatory diseases including psoriasis, asthma, and atherosclerosis. A suitable 5-lipoxygenase inhibitor might be useful for preventing and improving the symptoms of leukotriene-related inflammatory diseases. Here, we investigate the mechanism underlying the anti-inflammatory effect of a proanthocyanidin found in red-kerneled rice. Red-kerneled rice proanthocyanidin exhibited potent mixed noncompetitive inhibition of 5-lipoxygenase, with an IC of 7.0 μM. This compound decreased leukotriene B production in rat basophilic leukemia-2H3 cells. In imiquimod-induced psoriasis-like mouse skin, topical application of the proanthocyanidin suppressed hyperplasia, decreased inflammatory cell infiltration, and down-regulated expression of the psoriasis-associated genes Il17a, Il22, S100a9, and Krt1. Lipid metabolome analysis by electrospray ionization mass spectrometry showed that red-kerneled rice proanthocyanidin treatment of psoriasis-like mouse skin dose-dependently decreased the production of leukotriene B but no other arachidonate metabolites. Red-kerneled rice proanthocyanidin inhibits 5-lipoxygenase, resulting in a decrease in leukotriene B production and psoriasis-like mouse skin inflammation. These results suggest that this proanthocyanidin may be therapeutically effective for treating leukotriene-related diseases.Copyright © 2020. Published by Elsevier Inc.
[Angioimmunoblastic T-cell lymphoma complicated with various autoimmune abnormalities and myelofibrosis].
March 12, 2020
Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism.
February 15, 2019
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