Morin Protects LPS-Induced Mastitis via Inhibiting NLRP3 Inflammasome and NF-κB Signaling Pathways

Inflammation. 2020 Aug;43(4):1293-1303. doi: 10.1007/s10753-020-01208-x.

Abstract

Mastitis is one of the most common diseases that both affects human and animals. Morin is derived from the member of Moraceae family, which has been used in the treatment of many inflammatory diseases. The purpose of this study was to test the protective effect of morin on LPS-induced mastitis and to clarify the possible mechanism. In vivo, the mastitis model was established by lipopolysaccharide (LPS), and morin was treated 1 h before stimulation of LPS. In vitro, peritoneal macrophages were used to test the regulation mechanisms of morin on mastitis. The inflammatory cytokines (TNF-α, IL-1β, and IL-6) was tested by ELISA. Myeloperoxidase (MPO) activity was measured by MPO kit. The expression of NLRP3 inflammasome and NF-κB signaling pathway proteins were detected by western blotting. The results showed that morin alleviated the pathological damage of mammary gland tissues, MPO activity, and the production of TNF-α, IL-1β, and IL-6 in mammary gland tissues. In vitro, morin significantly suppressed the production of inflammatory cytokines. In addition, it also inhibited the activation of NLRP3 inflammasome and NF-κB signaling pathway induced by LPS. In conclusion, the present study suggested that the protective effect of morin against LPS-induced mastitis may be due to its ability to inhibit NLRP3 inflammasome expression and NF-κB signaling pathway.

Keywords: LPS; NF-κB; NLRP3 inflammasome; mastitis; morin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Female
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Lipopolysaccharides / toxicity*
  • Mastitis / chemically induced
  • Mastitis / metabolism
  • Mastitis / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Antioxidants
  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • morin