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佩米诺宁通过抑制 AKT/NF-κB、ERK1/2 和 p38 信号通路来预防脂多糖诱导的乳腺炎。

Peiminine Protects against Lipopolysaccharide-Induced Mastitis by Inhibiting the AKT/NF-κB, ERK1/2 and p38 Signaling Pathways.

机构信息

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

出版信息

Int J Mol Sci. 2018 Sep 6;19(9):2637. doi: 10.3390/ijms19092637.

Abstract

Peiminine, an alkaloid extracted from Fritillaria plants, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effect of peiminine on a mouse lipopolysaccharide (LPS)-induced mastitis model remains to be elucidated. The purpose of this experiment was to investigate the effect of peiminine on LPS-induced mastitis in mice. LPS was injected through the canals of the mammary gland to generate the mouse LPS-induced mastitis model. Peiminine was administered intraperitoneally 1 h before and 12 h after the LPS injection. In vitro, mouse mammary epithelial cells (mMECs) were pretreated with different concentrations of peiminine for 1 h and were then stimulated with LPS. The mechanism of peiminine on mastitis was studied by hematoxylin-eosin staining (H&E) staining, western blotting, and enzyme-linked immunosorbent assay (ELISA). The results showed that peiminine significantly decreased the histopathological impairment of the mammary gland in vivo and reduced the production of pro-inflammatory mediators in vivo and in vitro. Furthermore, peiminine inhibited the phosphorylation of the protein kinase B (AKT)/ nuclear factor-κB (NF-κB), extracellular regulated protein kinase (ERK1/2), and p38 signaling pathways both in vivo and in vitro. All the results suggested that peiminine exerted potent anti-inflammatory effects on LPS-induced mastitis in mice. Therefore, peiminine might be a potential therapeutic agent for mastitis.

摘要

冬凌草甲素是从贝母属植物中提取的一种生物碱,具有很强的抗炎作用。然而,冬凌草甲素对脂多糖(LPS)诱导的乳腺炎模型的抗炎作用尚未阐明。本实验旨在研究冬凌草甲素对 LPS 诱导的乳腺炎的影响。通过乳腺管内注射 LPS 建立小鼠 LPS 诱导的乳腺炎模型。在 LPS 注射前 1 h 和注射后 12 h 经腹腔给予冬凌草甲素。在体外,用不同浓度的冬凌草甲素预处理小鼠乳腺上皮细胞(mMEC)1 h,然后用 LPS 刺激。通过苏木精-伊红(H&E)染色、Western blot 和酶联免疫吸附试验(ELISA)研究冬凌草甲素对乳腺炎的作用机制。结果表明,冬凌草甲素显著减轻了体内乳腺组织的组织病理学损伤,减少了体内和体外促炎介质的产生。此外,冬凌草甲素抑制了 AKT/NF-κB 和 ERK1/2/p38 信号通路的磷酸化,无论是在体内还是在体外。所有结果表明,冬凌草甲素对 LPS 诱导的乳腺炎具有很强的抗炎作用。因此,冬凌草甲素可能是乳腺炎的一种潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d67/6164606/ae4ce8483a53/ijms-19-02637-g001.jpg

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