Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

Phytomedicine. 2014 Jul-Aug;21(8-9):1053-61. doi: 10.1016/j.phymed.2014.04.011. Epub 2014 May 20.

Abstract

Purpose: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells.

Methods: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism.

Results: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells.

Conclusion: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.

Keywords: Atopic dermatitis; HO-1; NF-κB; Platycodon grandiflorum; STAT1; Saponins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Allergic Agents / chemistry
  • Anti-Allergic Agents / isolation & purification
  • Anti-Allergic Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Dinitrochlorobenzene / adverse effects
  • Gene Expression Regulation
  • Genes, Reporter
  • Heme Oxygenase-1 / drug effects
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Immunoglobulin E / blood
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Mice
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • Platycodon / chemistry*
  • STAT1 Transcription Factor / drug effects
  • STAT1 Transcription Factor / metabolism
  • Saponins / chemistry
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • Anti-Allergic Agents
  • Changkil
  • Cytokines
  • Dinitrochlorobenzene
  • Membrane Proteins
  • NF-kappa B
  • Plant Extracts
  • STAT1 Transcription Factor
  • Saponins
  • Stat1 protein, mouse
  • Triterpenes
  • Immunoglobulin E
  • platycodin D
  • Heme Oxygenase-1
  • Hmox1 protein, mouse