Malabaricone C derived from nutmeg inhibits arachidonate 5-lipoxygenase activity and ameliorates psoriasis-like skin inflammation in mice
Malabaricone C derived from nutmeg inhibits arachidonate 5-lipoxygenase activity and ameliorates psoriasis-like skin inflammation in mice
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源自肉豆蔻的 Malabaricone C 抑制花生四烯酸 5-脂氧合酶活性并改善小鼠牛皮癣样皮肤炎症
DOI：
10.1016/j.freeradbiomed.2022.09.028
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发表时间：
2022
影响因子：
7.4
通讯作者：
Suzuki-Yamamoto Toshiko
中科院分区：
文献类型：
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作者：
Tsukayama Izumi;Kawakami Yuki;Tamenobu Asako;Toda Keisuke;Maruoka Saya;Nagasaki Yuki;Mori Yoshiko;Sawazumi Risa;Okamoto Kensuke;Kanzaki Keita;Ito Hideyuki;Takahashi Yoshitaka;Miki Yoshimi;Yamamoto Kei;Murakami Makoto;Suzuki-Yamamoto Toshiko
作为促炎脂质介质，白三烯在包括银屑病在内的多种炎性疾病中具有病理生理活性。在从花生四烯酸生物合成白三烯的过程中，5-脂氧合酶催化前两步。在本研究中，我们发现肉豆蔻（肉豆蔻）强烈抑制5-脂氧合酶的催化活性。为了表征肉豆蔻的生物活性成分，我们对肉豆蔻的含水乙醇提取物进行了5-脂氧合酶抑制活性引导的分级，从而分离出具有抗氧化活性的malabaricone C。Malabaricone C对5-脂氧合酶表现出强效竞争性抑制作用，IC 50值为0.2 μM。在咪喹莫特诱导的银屑病样皮肤病变小鼠中，局部应用2 mM malabaricone C可显著改善增生和炎性细胞浸润，并抑制银屑病相关基因S100 a9、Krt 1、Il 17 a和Il 22的表达。这些银屑病样皮肤病变的脂质代谢组学分析显示，马拉巴硅油C显著降低了白三烯B4的水平，但没有显著增加其他促炎脂质介质。这些结果表明，马拉巴硅油C通过抑制5-脂氧合酶降低LTB 4，并改善银屑病样皮肤炎症的症状。
As pro-inflammatory lipid mediators, leukotrienes have pathophysiological activities in several inflammatory diseases, including psoriasis. In the biosynthesis of leukotrienes from arachidonic acid, 5-lipoxygenase catalyzes the first two steps. In the present study, we showed that nutmeg (Myristica fragrans) strongly inhibited the catalytic activity of 5-lipoxygenase. To characterize the bioactive component(s) of nutmeg, we performed 5-lipoxygenase inhibitory activity-guided fractionation of aqueous ethanol extract of nutmeg, resulting in the isolation of malabaricone C having antioxidant activity. Malabaricone C exhibited potent competitive inhibition of 5-lipoxygenase with an IC50value of 0.2 μM. In mice with imiquimod-induced psoriasis-like skin lesions, topical application of 2 mM malabaricone C significantly ameliorated hyperplasia and inflammatory cell infiltration, and suppressed the expression of the psoriasis-associated genesS100a9,Krt1,Il17a, andIl22. Lipid metabolome analysis of these psoriasis-like skin lesions showed that malabaricone C markedly decreased the level of leukotriene B4but did not significantly increase the other pro-inflammatory lipid mediators. These findings suggest that malabaricone C decreases LTB4by the 5-lipoxygenase inhibition and ameliorates the symptoms of psoriasis-like skin inflammation.