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

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

  • J Anim Sci Biotechnol. 2023 May 3;14(1):61. doi: 10.1186/s40104-023-00858-9.
Dan Shao 1,  Wenxiang Shen 1 2,  Yuyang Miao 1,  Zhen Gao 1,  Menghao Pan 1,  Qiang Wei 1,  Zuoting Yan 1 2,  Xiaoe Zhao 3,  Baohua Ma 4
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
  • 2 Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Science, Lanzhou, 730050, China.
  • 3 Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China. [email protected].
  • 4 Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China. [email protected].
PMID: 37131202 DOI: 10.1186/s40104-023-00858-9
Abstract

Background: Mastitis 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.

Results: In vitro, SFN downregulated the mRNA expression of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β 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-κB) 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.

Conclusions: These 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.

Keywords

Autophagy; Goat mammary epithelial cells; Inflammation; Nrf2; Oxidative stress; Sulforaphane.

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