Abstract

Atopic dermatitis (AD) is an allergic and chronic inflammatory skin disease. The present study investigates the anti-allergic, antioxidant, and anti-inflammatory activities of the ethanolic extract of Cornus officinalis (COFE) for possible applications in the treatment of AD. COFE inhibits the release of β-hexosaminidase from RBL-2H3 cells sensitized with the dinitrophenyl-immunoglobulin E (IgE-DNP) antibody after stimulation with dinitrophenyl-human serum albumin (DNP-HSA) in a concentration-dependent manner (IC50 = 0.178 mg/mL). Antioxidant activity determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power assay, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, result in EC50 values of 1.82, 10.76, and 0.6 mg/mL, respectively. Moreover, the extract significantly inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the mRNA expression of iNOS and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) through attenuation of NF-κB activation in RAW 264.7 cells. COFE significantly inhibits TNF-α-induced apoptosis in HaCaT cells without cytotoxic effects (p < 0.05). Furthermore, 2-furancarboxaldehyde and loganin are identified by gas chromatography/mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, respectively, as the major compounds. Molecular docking analysis shows that loganin, cornuside, and naringenin 7-O-β-D-glucoside could potentially disrupt the binding of IgE to human high-affinity IgE receptors (FceRI). Our results suggest that COFE might possess potential inhibitory effects on allergic responses, oxidative stress, and inflammatory responses.

Highlights

  • Atopic dermatitis (AD) is an allergic and chronic skin inflammation condition characterized by pruritic eczema and mechanical skin injury caused by scratching, elevated serum IgE levels, and markedly increased immune cells levels [1]

  • The IC50 value of COFEofficinalis (left) and (COFE) for β-hexosaminidase release inhibition was 0.178 mg/mL, showing that the potential anti-atopic activity occurred through the suppression of the IgE-induced degranulation of RBL-2H3 cells

  • COFE consistently suppresses the expression of IL-1β, IL-6, and TNF-α, suggesting that the upstream signaling molecules could be the determining step in the anti-inflammatory response induced by COFE (Figure 4)

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Summary

Introduction

Atopic dermatitis (AD) is an allergic and chronic skin inflammation condition characterized by pruritic eczema and mechanical skin injury caused by scratching, elevated serum IgE levels, and markedly increased immune cells levels (eosinophils, mast cells, and lymphocytes) [1]. Th2 cells release cytokines such as interleukin (IL)-4, IL-5, IL-10, and IL-13, resulting in the activation and proliferation of eosinophils and mast cells. The resultant itching, skin scratching, mechanical skin barrier injury, and activation of immune cells, lead to further Th2 cell activation and itching [3]. Cornus officinalis is a dogwood species native to Eastern Asia (Korea, China, and Japan). The protective effect of C. officinalis, used in herbal mixture with four other plant extracts, against atopic dermatitis in BALB/C mice was recently reported [5]. The major component of the reported herbal mixture was

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