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Red-kerneled Rice Proanthocyanidin Inhibits Arachidonate 5-lipoxygenase and Decreases Psoriasis-Like Skin Inflammation

Keisuke Toda, Izumi Tsukayama, Yuki Nagasaki, Yuka Konoike, Asako Tamenobu, Natsuki Ganeko, Hideyuki Ito, Yuki Kawakami, Yoshitaka Takahashi, Yoshimi Miki, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto

Arch Biochem Biophys. 2020 Feb 27;108307.

PMID: 32112739

Abstract:

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 human and rat 5-lipoxygenases, with an IC50 values of 15.1 μM against human enzyme, and 7.0 μM against rat enzyme, respectively. This compound decreased leukotriene B4 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 B4 but no other arachidonate metabolites. Red-kerneled rice proanthocyanidin inhibits 5-lipoxygenase, resulting in a decrease in leukotriene B4 production and psoriasis-like mouse skin inflammation. These results suggest that this proanthocyanidin may be therapeutically effective for treating leukotriene-related diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP99010636 Imiquimod Related Compound B Imiquimod Related Compound B 99010-63-6 Price
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