Farrerol Relieve Lipopolysaccharide (LPS)-Induced Mastitis by Inhibiting AKT/NF-κB p65, ERK1/2 and P38 Signaling Pathway.
Farrerol Relieve Lipopolysaccharide (LPS)-Induced Mastitis by Inhibiting AKT/NF-κB p65, ERK1/2 and P38 Signaling Pathway.
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DOI：
10.3390/ijms19061770
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发表时间：
2018-06-14
影响因子：
5.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Li Y;Gong Q;Guo W;Kan X;Xu D;Ma H;Fu S;Liu J
Farrerol已被证明具有抗炎作用。然而，法拉罗对乳房炎的影响还没有被研究。本研究旨在探讨法雷罗对内毒素诱导的小鼠乳房炎和内毒素诱导的小鼠乳腺上皮细胞炎症反应的影响及其机制。体内注射脂多糖建立小鼠乳房炎模型，观察法拉罗对乳房炎小鼠的组织病理学改变、炎症反应及蛋白激酶B、核因子-kappaBp65(NF-κBp65)、p38、细胞外调节蛋白激酶(ERK1/2)的激活程度的影响。体外培养的微血管内皮细胞先用法瑞罗孵育1h，再用脂多糖刺激，检测炎症反应及相关的信号转导途径。体内实验结果表明，法瑞罗能改善乳腺病理损伤，减轻髓过氧化物酶活性，抑制促炎介质的产生，抑制AKT、NF-κB p65、p38和ERK1/2的磷酸化。体外实验还发现法瑞罗还能抑制炎症反应及相关的信号转导途径。综上所述，本研究揭示了法雷罗通过下调AKT、NF-κB p65、p38和ERK1/2的磷酸化来抑制炎症反应，从而抑制脂多糖诱导的乳房炎的进一步发展。这些结果表明，法拉罗可能被用作乳房炎的抗炎药物。
Farrerol has been proved to have an anti-inflammatory effect. However, the effects of farrerol on mastitis have not been investigated. This study was aimed to investigate the effect and mechanism of farrerol in lipopolysaccharide (LPS)-induced mouse mastitis and LPS-induced inflammatory response of mouse mammary epithelial cells (mMECs). In vivo, LPS were injected to the tetrad pair of nipples for establishing mouse mastitis, and then tested the effect of farrerol on histopathological changes, inflammatory response and activation degree of protein kinase B (AKT), nuclear factor-kappa B p65 (NF-κB p65), p38, extracellular regulated protein kinase (ERK1/2). In vitro, the mMECs were incubated by farrerol for 1 h following by stimulating with LPS, and then the inflammatory response and the related signaling pathways were detected. The in vivo results found that farrerol could improve pathological injury of mammary gland, attenuate the activity of myeloperoxidase (MPO), inhibit the production of pro-inflammatory mediators and the phosphorylation of AKT, NF-κB p65, p38 and ERK1/2. The in vitro results also found farrerol inhibited inflammatory response and the related signaling pathways. Collectively, this study revealed that farrerol inhibits the further development of LPS-induced mastitis by inhibiting inflammatory response via down regulating phosphorylation of AKT, NF-κB p65, p38, and ERK1/2. These findings suggest that farrerol may be used as an anti-inflammatory drug for mastitis.
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