Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes.

Abstract

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C₄ (LTC₄) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC₄ by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.

• Authors: Seong Eun Jin, Hyekyung Ha, Hyeun-Kyoo Shin, Chang-Seob Seo
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 2 (Jan 11 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 30642008 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Anti-Inflammatory Agents
• Biomarkers
• Chemokines
• Flavonoids
• NF-kappa B
• STAT1 Transcription Factor
• STAT1 protein, human
• morusin
• kuwanon G

Topics

• Anti-Allergic Agents (chemistry, pharmacology)
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Biomarkers
• Cell Line
• Chemokines (metabolism)
• Chromatography, High Pressure Liquid
• Flavonoids (chemistry, pharmacology)
• Humans
• Keratinocytes (drug effects, metabolism)
• Mast Cells (drug effects, metabolism)
• Molecular Structure
• NF-kappa B (metabolism)
• Phosphorylation
• STAT1 Transcription Factor (metabolism)