Effects of Hovenia Dulcis Thunb. Extract and Methyl Vanillate on Atopic Dermatitis-Like Skin Lesions and TNF-α/IFN-γ-induced Chemokines Production in HaCaT Cells

J Pharm Pharmacol. 2016 Nov;68(11):1465-1479. doi: 10.1111/jphp.12640. Epub 2016 Oct 2.

Abstract

Objectives: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells.

Methods: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically.

Key findings: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells.

Conclusion: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.

Keywords: Hovenia dulcis; NC/Nga mice; Th1-/Th2-related mediators; atopic dermatitis; immunoglobulin E; immunoglobulin G2a.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / metabolism
  • Chemokines / blood
  • Chemokines / immunology
  • Chemokines / metabolism*
  • Dermatitis, Atopic / blood
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / prevention & control*
  • Dinitrochlorobenzene
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Interferon-gamma / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rhamnaceae / chemistry*
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1-Th2 Balance / drug effects
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transcription Factors / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vanillic Acid / analogs & derivatives*
  • Vanillic Acid / isolation & purification
  • Vanillic Acid / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • CCL17 protein, human
  • CCL22 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokines
  • Immunoglobulin G
  • Plant Extracts
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • methyl vanillate
  • Immunoglobulin E
  • Interferon-gamma
  • Mitogen-Activated Protein Kinases
  • Dinitrochlorobenzene
  • Vanillic Acid