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小檗胺通过抑制NF-κB和MAPK信号通路发挥抗炎作用。

Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways.

作者信息

Jia Xiao-Jian, Li Xi, Wang Feng, Liu Han-Qing, Zhang Da-Jun, Chen Yun

机构信息

Shenzhen Kangning Hospital & Shenzhen Mental Health Center, Shenzhen, China.

Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.

出版信息

Cell Physiol Biochem. 2017;41(6):2307-2318. doi: 10.1159/000475650. Epub 2017 Apr 26.

Abstract

BACKGROUND/AIMS: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms.

METHODS

Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation.

RESULTS

BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages.

CONCLUSIONS

Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

摘要

背景/目的:本研究旨在探讨从黄柏(小檗胺)中提取的双苄基异喹啉生物碱小檗胺(BER)的抗炎活性及其潜在机制。

方法

体外将巨噬细胞和中性粒细胞用BER处理,并用脂多糖(LPS)和N-甲酰甲硫氨酸-亮氨酸-苯丙氨酸(fMLP)刺激。用定量逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)评估BER对巨噬细胞中促炎介质表达的影响。用流式细胞术和WST-1还原试验测定BER对中性粒细胞活化和超氧化物释放的影响。通过蛋白质印迹分析评估BER对巨噬细胞中与炎症反应相关信号通路激活的抑制作用。此外,通过腹腔注射巯基乙酸盐培养基建立小鼠腹膜炎模型,并通过促炎因子产生和白细胞渗出的定量分析在体内研究BER的抗炎作用。

结果

BER显著抑制LPS刺激的巨噬细胞中炎症因子的表达,并抑制fMLP刺激的中性粒细胞的活化和超氧化物释放。在小鼠腹膜炎模型中,BER显著抑制巨噬细胞的活化和中性粒细胞的渗出。分析表明,BER显著抑制LPS刺激的巨噬细胞中核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK,包括c-Jun氨基末端激酶(JNK)和细胞外信号调节激酶1/2(ERK1/2))信号通路的磷酸化。

结论

总体而言,本研究数据表明BER具有抗炎潜力,其通过抑制NF-κB和MAPK信号通路发挥作用,因此有望用于治疗炎症性疾病。

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