期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 689, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2020.108307
关键词
Anti-inflammation; Arachidonate 5-lipoxygenase; Leukotriene B-4; Psoriasis; Red-kerneled rice proanthocyanidin
资金
- Japan Society for the Promotion of Science KAKENHI (Tokyo, Japan) [18K11134]
- Public Foundation of Elizabeth Arnold-Fuji (Nagoya, Japan)
- Wesco Scientific Promotion Foundation (Okayama, Japan)
- Japan Agency for Medical Research and Development-FORCE (Tokyo, Japan)
- Grants-in-Aid for Scientific Research [18K11134] Funding Source: KAKEN
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 mu M against human enzyme, and 7.0 mu M against rat enzyme, respectively. This compound decreased leukotriene B-4 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-4 but no other arachidonate metabolites. Red-kerneled rice proanthocyanidin inhibits 5-lipoxygenase, resulting in a decrease in leukotriene B-4 production and psoriasis-like mouse skin inflammation. These results suggest that this proanthocyanidin may be therapeutically effective for treating leukotriene-related diseases.
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