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吴茱萸碱通过抑制AKT/NF-κB p65和MAPK信号通路缓解脂多糖诱导的乳腺炎。

Evodiamine Relieve LPS-Induced Mastitis by Inhibiting AKT/NF-κB p65 and MAPK Signaling Pathways.

作者信息

Yang Yuanxi, Ran Xin, Wang Hefei, Chen Yingsheng, Hou Shuang, Yang Zhanqing, Fu Shoupeng, Liu Juxiong, Hu Guiqiu, Guo Wenjin

机构信息

Department of Theoretic Veterinary Medicine, College of Veterinary Medicine, Jilin University, Jilin, Changchun, 130062, China.

出版信息

Inflammation. 2022 Feb;45(1):129-142. doi: 10.1007/s10753-021-01533-9. Epub 2021 Aug 16.

Abstract

Evodiamine, an alkaloid component in the fruit of Evodia, has been shown to have biological functions such as antioxidant and anti-inflammatory. But whether evodiamine plays an improvement role on mastitis has not been studied. To investigate the effect and mechanism of evodiamine on lipopolysaccharide (LPS)-induced mastitis was the purpose of this study. In animal experiments, the mouse mastitis model was established by injecting LPS into the canals of the mammary gland. The results showed that evodiamine could significantly relieve the pathological injury of breast tissue and the production of pro-inflammatory cytokines and inhibit the activation of inflammation-related pathways such as AKT, NF-κB p65, ERK1/2, p38, and JNK. In cell experiments, the mouse mammary epithelial cells (mMECs) were incubated with evodiamine for 1 h and then stimulated with LPS. Next, pro-inflammatory mediators and inflammation-related signal pathways were detected. As expected, our results showed that evodiamine notably ameliorated the inflammatory reaction and inhibit the activation of related signaling pathways of mMECs. All the results suggested that evodiamine inhibited inflammation by inhibiting the phosphorylation of AKT, NF-κBp65, ERK1/2, p38, and JNK thus the LPS-induced mastitis was ameliorated. These findings suggest that evodiamine maybe a potential drug for mastitis because of its anti-inflammatory effects.

摘要

吴茱萸碱是吴茱萸果实中的一种生物碱成分,已被证明具有抗氧化和抗炎等生物学功能。但吴茱萸碱对乳腺炎是否具有改善作用尚未见研究报道。本研究旨在探讨吴茱萸碱对脂多糖(LPS)诱导的乳腺炎的影响及其作用机制。在动物实验中,通过向乳腺导管内注射LPS建立小鼠乳腺炎模型。结果显示,吴茱萸碱可显著减轻乳腺组织的病理损伤和促炎细胞因子的产生,并抑制AKT、NF-κB p65、ERK1/2、p38和JNK等炎症相关信号通路的激活。在细胞实验中,将小鼠乳腺上皮细胞(mMECs)与吴茱萸碱孵育1小时后,再用LPS刺激,然后检测促炎介质和炎症相关信号通路。不出所料,我们的结果表明,吴茱萸碱显著改善了炎症反应,并抑制了mMECs相关信号通路的激活。所有结果表明,吴茱萸碱通过抑制AKT、NF-κBp65、ERK1/2、p38和JNK的磷酸化来抑制炎症,从而改善LPS诱导的乳腺炎。这些研究结果表明,吴茱萸碱因其抗炎作用可能是一种治疗乳腺炎的潜在药物。

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