| RRC ID |
67066
|
| 著者 |
Toda K, Tsukayama I, Nagasaki Y, Konoike Y, Tamenobu A, Ganeko N, Ito H, Kawakami Y, Takahashi Y, Miki Y, Yamamoto K, Murakami M, Suzuki-Yamamoto T.
|
| タイトル |
Red-kerneled rice proanthocyanidin inhibits arachidonate 5-lipoxygenase and decreases psoriasis-like skin inflammation.
|
| ジャーナル |
Arch Biochem Biophys
|
| 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.
|
| 巻・号 |
689
|
| ページ |
108307
|
| 公開日 |
2020-8-15
|
| DOI |
10.1016/j.abb.2020.108307
|
| PII |
S0003-9861(19)30833-1
|
| PMID |
32112739
|
| MeSH |
Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / therapeutic use*
Arachidonate 5-Lipoxygenase / metabolism*
Cell Line
Humans
Inflammation / drug therapy
Inflammation / metabolism
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / therapeutic use*
Male
Mice, Inbred BALB C
Oryza / chemistry
Proanthocyanidins / chemistry
Proanthocyanidins / therapeutic use*
Psoriasis / drug therapy*
Psoriasis / metabolism
Rats
|
| IF |
3.391
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
