Isorhamnetin ameliorates LPS-induced inflammatory response through downregulation of NF-κB signaling

Inflammation. 2016 Aug;39(4):1291-301. doi: 10.1007/s10753-016-0361-z.

Abstract

Isorhamnetin, a flavonoid mainly found in Hippophae fhamnoides L. fruit, has been known for its antioxidant activity and its ability to regulate immune response. In this study, we investigated whether isorhamnetin exerts potent antiinflammatory effects in RAW264.7 cell and mouse model stimulated by LPS. The cytokine (TNF-α, IL-1β, and IL-6) levels were determined. In the mouse model of acute lung injury, the phosphorylation of NF-κB proteins was analyzed and inhibitor of NF-κB signaling (PDTC) was used on mice. Our results showed that isorhamnetin markedly decreased TNF-α, IL-1β, and IL-6 concentrations and suppressed the activation of NF-κB signaling. Meanwhile, isorhamnetin reduced the amount of inflammatory cells, the lung wet-to-dry weight ratio, protein leakage, and myeloperoxidase activity. Interference with specific inhibitor revealed that isorhamnetin-mediated suppression of cytokines and protein was via NF-κB signaling. So, it suggests that isorhamnetin might be a potential therapeutic agent for preventing inflammatory diseases.

Keywords: NF-κB; acute lung injury; cytokines; isorhamnetin.

MeSH terms

  • Acute Lung Injury / pathology
  • Animals
  • Antioxidants / pharmacology
  • Cytokines / drug effects
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Inflammation / drug therapy
  • Inflammation / prevention & control*
  • Lipopolysaccharides
  • Mice
  • NF-kappa B / metabolism*
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects

Substances

  • Antioxidants
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • 3-methylquercetin
  • Quercetin