Sulforaphane prevents LPS-induced inflammation by regulating the Nrf2-mediated autophagy pathway in goat mammary epithelial cells and a mouse model of mastitis

文献类型： 外文期刊

第一作者： Shao, Dan

作者： Shao, Dan;Shen, Wenxiang;Miao, Yuyang;Gao, Zhen;Pan, Menghao;Wei, Qiang;Yan, Zuoting;Zhao, Xiaoe;Ma, Baohua;Shen, Wenxiang;Yan, Zuoting

作者机构：

关键词： Autophagy; Goat mammary epithelial cells; Inflammation; Nrf2; Oxidative stress; Sulforaphane

期刊名称：JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY （ 影响因子：7.0； 五年影响因子：7.3 ）

ISSN： 1674-9782

年卷期： 2023 年 14 卷 1 期

页码：

收录情况： SCI

摘要： BackgroundMastitis not only deteriorates the composition or quality of milk, but also damages the health and productivity of dairy goats. Sulforaphane (SFN) is a phytochemical isothiocyanate compound with various pharmacological effects such as anti-oxidant and anti-inflammatory. However, the effect of SFN on mastitis has yet to be elucidated. This study aimed to explore the anti-oxidant and anti-inflammatory effects and potential molecular mechanisms of SFN in lipopolysaccharide (LPS)-induced primary goat mammary epithelial cells (GMECs) and a mouse model of mastitis.ResultsIn vitro, SFN downregulated the mRNA expression of inflammatory factors (tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6), inhibited the protein expression of inflammatory mediators (cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS)) while suppressing nuclear factor kappa-B (NF-kappa B) activation in LPS-induced GMECs. Additionally, SFN exhibited an antioxidant effect by increasing Nrf2 expression and nuclear translocation, up-regulating antioxidant enzymes expression, and decreasing LPS-induced reactive oxygen species (ROS) production in GMECs. Furthermore, SFN pretreatment promoted the autophagy pathway, which was dependent on the increased Nrf2 level, and contributed significantly to the improved LPS-induced oxidative stress and inflammatory response. In vivo, SFN effectively alleviated histopathological lesions, suppressed the expression of inflammatory factors, enhanced immunohistochemistry staining of Nrf2, and amplified of LC3 puncta LPS-induced mastitis in mice. Mechanically, the in vitro and in vivo study showed that the anti-inflammatory and anti-oxidative stress effects of SFN were mediated by the Nrf2-mediated autophagy pathway in GMECs and a mouse model of mastitis.ConclusionsThese results indicate that the natural compound SFN has a preventive effect on LPS-induced inflammation through by regulating the Nrf2-mediated autophagy pathway in primary goat mammary epithelial cells and a mouse model of mastitis, which may improve prevention strategies for mastitis in dairy goats.

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