Modulation of HMGB1 translocation and RAGE/NFκB cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice

Exp Dermatol. 2015 Jun;24(6):418-23. doi: 10.1111/exd.12685. Epub 2015 Mar 25.


Quercetin, glycosylated form of flavonoid compound, has potent antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of quercetin on skin lesion, high-mobility group box (HMGB)1 cascade signalling and inflammation in atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga transgenic mouse. After AD induction, quercetin (50 mg/kg, p.o) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)4, nuclear factor (NF)κB, nuclear factor erythroid-2-related factor (Nrf)2, kelch-like ECH-associated protein (Keap)1, extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, IL-4) were measured by enzyme-linked immunosorbent assay. Quercetin treatment attenuated the development of AD-like skin lesions. Histological analysis showed that quercetin inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells. Furthermore, quercetin treatment downregulated cytoplasmic HMGB1, RAGE, nuclear p-NFκB, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4 and upregulated nuclear Nrf2. Our data demonstrated that the HMGB1/RAGE/NFκB signalling might play an important role in skin inflammation, and quercetin treatment could be a promising agent for AD by modulating the HMGB1/RAGE/NFκB signalling and induction of Nrf2 protein.

Keywords: cytokine; high-mobility group box protein 1; nuclear factor kappa B; quercetin; receptor for advanced glycation products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / etiology
  • Dermatitis, Atopic / physiopathology
  • Dermatophagoides farinae / pathogenicity
  • Disease Models, Animal
  • Female
  • HMGB1 Protein / drug effects
  • HMGB1 Protein / genetics*
  • HMGB1 Protein / physiology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mice, Transgenic
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / physiology
  • NF-kappa B / drug effects
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • Quercetin / pharmacology*
  • Quercetin / therapeutic use
  • Receptor for Advanced Glycation End Products / drug effects
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / physiology*
  • Severity of Illness Index
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Skin / drug effects
  • Skin / pathology
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology
  • Translocation, Genetic / drug effects*
  • Translocation, Genetic / genetics
  • Translocation, Genetic / physiology


  • Antioxidants
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Receptor for Advanced Glycation End Products
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Quercetin