Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama, 719-1197, Japan.
Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama, 719-1197, Japan; Department of Nutrition and Life Science, Fukuyama University, Sanzo, Gakuen-cho 1, Fukuyama, Hiroshima, 729-0292, Japan.
Arch Biochem Biophys. 2020 Aug 15;689:108307. doi: 10.1016/j.abb.2020.108307. Epub 2020 Feb 27.
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 IC values of 15.1 μM against human enzyme, and 7.0 μM against rat enzyme, respectively. 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.
5-脂氧合酶是花生四烯酸合成白三烯的关键酶。产生的白三烯参与炎症性疾病，包括银屑病、哮喘和动脉粥样硬化。合适的 5-脂氧合酶抑制剂可能有助于预防和改善与白三烯相关的炎症性疾病的症状。在这里，我们研究了红米中原花青素的抗炎作用机制。红米原花青素对人和大鼠 5-脂氧合酶表现出强烈的混合非竞争性抑制作用，对人酶的 IC 值为 15.1 μM，对大鼠酶的 IC 值为 7.0 μM。该化合物减少了大鼠嗜碱性白血病-2H3 细胞中白三烯 B 的产生。在咪喹莫特诱导的银屑病样小鼠皮肤中，原花青素的局部应用抑制了过度增生，减少了炎症细胞浸润，并下调了银屑病相关基因 Il17a、Il22、S100a9 和 Krt1 的表达。电喷雾电离质谱的脂质代谢组学分析表明，红米原花青素处理银屑病样小鼠皮肤可剂量依赖性降低白三烯 B 的产生，但不影响其他花生四烯酸代谢物。红米原花青素抑制 5-脂氧合酶，导致白三烯 B 产生减少和银屑病样小鼠皮肤炎症。这些结果表明，这种原花青素可能对治疗与白三烯相关的疾病具有治疗效果。
