Nuciferine alleviates LPS-induced mastitis in mice via suppressing the TLR4-NF-κB signaling pathway

Inflamm Res. 2018 Dec;67(11-12):903-911. doi: 10.1007/s00011-018-1183-2. Epub 2018 Aug 25.

Abstract

Background: Nuciferine, a major bioactive component from the lotus leaf, has been reported to have notable anti-inflammatory activities such as renal inflammation and acute lung injury in previous studies. Mastitis is one of the most prevalent diseases in the dairy cattle, which causes large economic losses for the dairy industry. However, the effects of nuciferine on lipopolysaccharide (LPS)-induced mastitis have not been reported.

Methods and results: Here, we investigated the anti-inflammatory effects of nuciferine on LPS-induced mastitis in mice and illuminated its potential mechanism on the TLR4-mediated signaling pathway in mouse mammary epithelial cells (mMECs). Histopathological changes and myeloperoxidase (MPO) activity assay showed that nuciferine treatment significantly alleviated the LPS-induced injury of mammary gland flocculus, inflammatory cells infiltration. qPCR and ELISA assays indicated that nuciferine dose-dependently reduced the levels of TNF-α and IL-1β, which indicated that nuciferine might have therapeutic effects on mastitis. Furthermore, nuciferine treatment significantly decreased the expression of TLR4 in a dose-dependent manner. Besides, nuciferine was also found to suppress LPS-induced NF-κB activation.

Conclusion: These findings indicate that nuciferine potently ameliorates LPS-induced mastitis by inhibition of the TLR4-NF-κB signaling pathway.

Keywords: Anti-inflammation; LPS; Mastitis; NF-κB; Nuciferine; TLR4.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use*
  • Aporphines / pharmacology*
  • Aporphines / therapeutic use*
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mastitis / chemically induced
  • Mastitis / drug therapy*
  • Mastitis / metabolism
  • Mastitis / pathology
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Aporphines
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • nuciferine