Vanillin protects the blood-milk barrier and inhibits the inflammatory response in LPS-induced mastitis in mice

Toxicol Appl Pharmacol. 2019 Feb 15:365:9-18. doi: 10.1016/j.taap.2018.12.022. Epub 2019 Jan 2.

Abstract

Vanillin is used in a variety of food, chemical, and pharmaceutical applications, and exhibits anti-inflammatory properties. However, there are no reports about the effects of vanillin on lipopolysaccharide (LPS)-induced mastitis. In this study, we explored the effects of vanillin on the subsequent inflammatory response and blood-milk barrier in LPS-induced mastitis. Results showed that vanillin suppressed the inflammatory response by a) inhibiting myeloperoxidase activity; b) decreasing the production of pro-inflammatory mediators which include tumor necrosis factor alpha (Tnf-α; from 128.5 ± 14.59 to 67.51 ± 10.88,pg/mL, P < 0.01), interleukin-6 (Il-6; from 531.5 ± 196.4 to 109.3 ± 24.14, pg/mL, P < 0.05), interleukin-1β (Il-1β; from 2569 ± 1648 to 731.8 ± 171.7, pg/mL, P < 0.05), inducible nitric oxide synthase (Inos), and cyclooxygenase-2 (Cox-2); and c) repairing the blood-milk barrier by increasing the protein levels of the tight junction proteins, including zona occludens 1 (Zo-1), claudin-3, and occludin. In vitro experiment, Vanillin can inhibit LPS-induced inflammation and enhance the protein levels of tight junction proteins. Further studies have shown that vanillin inhibits inflammation by inhibiting mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. Our findings showed that vanillin protects mammary gland from LPS-induced mastitis by enhancing the blood-milk barrier and inhibiting the inflammatory response.

Keywords: Blood–Milk Barrier; MAPK; Mastitis; NF-κB; Vanillin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Benzaldehydes / pharmacology*
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Lactation
  • Lipopolysaccharides*
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / immunology
  • Mammary Glands, Animal / metabolism
  • Mastitis / chemically induced
  • Mastitis / drug therapy*
  • Mastitis / immunology
  • Mastitis / metabolism
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxidase / metabolism
  • Pregnancy
  • Signal Transduction / drug effects
  • Tight Junction Proteins / metabolism
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzaldehydes
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Tight Junction Proteins
  • vanillin
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases