College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Int J Mol Sci. 2018 Jun 14;19(6):1770. doi: 10.3390/ijms19061770.
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.
法呢醇已被证明具有抗炎作用。然而，法呢醇对乳腺炎的作用尚未得到研究。本研究旨在探讨法呢醇对脂多糖（LPS）诱导的小鼠乳腺炎和 LPS 诱导的小鼠乳腺上皮细胞（mMEC）炎症反应的作用及机制。在体内，通过向四对乳头注射 LPS 建立小鼠乳腺炎模型，然后检测法呢醇对组织病理学变化、炎症反应和蛋白激酶 B（AKT）、核因子-κB p65（NF-κB p65）、p38、细胞外调节蛋白激酶（ERK1/2）激活程度的影响。在体外，用 LPS 刺激前先用法呢醇孵育 mMECs 1 h，然后检测炎症反应和相关信号通路。体内结果发现，法呢醇可改善乳腺组织的病理损伤，降低髓过氧化物酶（MPO）活性，抑制促炎介质的产生和 AKT、NF-κB p65、p38 和 ERK1/2 的磷酸化。体外结果也发现法呢醇抑制了炎症反应和相关信号通路。综上所述，本研究表明，法呢醇通过下调 AKT、NF-κB p65、p38 和 ERK1/2 的磷酸化抑制 LPS 诱导的乳腺炎的进一步发展，从而抑制炎症反应。这些发现提示法呢醇可能可作为一种治疗乳腺炎的抗炎药物。
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