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科罗索酸通过抑制巨噬细胞中IRAK-1的磷酸化来改善急性炎症。

Corosolic acid ameliorates acute inflammation through inhibition of IRAK-1 phosphorylation in macrophages.

作者信息

Kim Seung-Jae, Cha Ji-Young, Kang Hye Suk, Lee Jae-Ho, Lee Ji Yoon, Park Jae-Hyung, Bae Jae-Hoon, Song Dae-Kyu, Im Seung-Soon

机构信息

Department of Physiology, Keimyung University School of Medicine, Daegu 42601, Korea.

Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999; Gachon Medical Research Institute, Gill Hospital, Incheon 21936, Korea.

出版信息

BMB Rep. 2016 May;49(5):276-81. doi: 10.5483/bmbrep.2016.49.5.241.

Abstract

Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor-associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation. [BMB Reports 2016; 49(5): 276-281].

摘要

科罗索酸(CA)是一种从大花紫薇(巴拿巴)叶中分离出的三萜类化合物,它通过核因子κB(NF-κB)级联反应调节白细胞介素受体相关激酶(IRAK)-2的磷酸化来发挥抗炎作用。然而,CA对内毒素休克的保护作用尚未见报道。脂多糖(LPS,200 ng/mL,30分钟)诱导IRAK-1磷酸化,而用CA(10 μM)处理可显著减弱这种作用。此外,CA还降低了骨髓来源的巨噬细胞(BMDMs)中炎性小体的主要成分NLRP3和凋亡相关斑点样蛋白(ASC)的蛋白水平。CA刺激下调了LPS通过激活IRAK-1诱导的炎性小体组装。用IκB-α抑制剂Bay11-7082处理对CA介导的IRAK-1激活抑制没有影响,这表明CA介导的IRAK-1磷酸化减弱独立于NF-κB信号传导。这些结果表明,CA可改善小鼠BMDMs中的急性炎症,并且CA可能作为预防急性炎症的药物制剂。[《BMB报告》2016年;49(5): 276 - 281]

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8e2/5070707/484030cc963c/BMB-49-276-g001.jpg

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