Abstract

Cordyceps militaris is a medicinal mushroom used to treat immune-related diseases in East Asia. We investigated the anti-inflammatory effect of the extract of C. militaris grown on germinated Rhynchosia nulubilis (GRC) fermented with Pediococcus pentosaceus ON89A isolated from onion (GRC-ON89A) in vivo as well as in vitro. The anti-inflammatory effect of GRC-ON89A was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol content (TPC) and total flavonoid content (TFC) in the GRC-ON89A ethanol extract were significantly increased compared to that in GRC. GRC-ON89A hexane fraction (GRC-ON89A-Hex) inhibited the release of nitric oxide (NO) compared to that of the LPS-treated control without cytotoxicity in LPS-stimulated RAW 264.7 macrophages. GRC-ON89A-Hex decreased the inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF)-α mRNA expression in LPS-stimulated RAW 264.7 macrophages. In addition, pre-treatment with GRC-ON89A-Hex significantly inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. To induce allergic contact dermatitis (ACD), 1-fluoro-2, 4-dinitrofluorobenzene (DNFB) was applied to the surface of the right ears of C57BL/6N mice. GRC-ON89A reduced the ear swelling and thickness in DNFB-induced ACD mice. This study demonstrates the potential usefulness of GRC-ON89A as an anti-inflammatory dietary supplement or drug.

Highlights

  • Allergic contact dermatitis (ACD), a chronic inflammatory skin disease, is a type IV delayedhypersensitivity response induced by sensitization to allergens that causes redness, edema, and dryness of the skin [1,2]

  • We quantified the levels of adenosine and cordycepin in germinated Rhynchosia nulubilis (GRC) and GRC-ON89A extract using gas chromatography-time-of-flight (GC-TOF) mass spectrometry (MS, Table 1)

  • The level of cordycepin in GRC-ON89A was higher than that in GRC (1053.33 ± 11.81 μg/g vs. 180.58 ± 1.54 μg/g, respectively). These results suggest that fermentation of GRC by P. pentosaceus ON89A affected the contents of representative molecules

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Summary

Introduction

Allergic contact dermatitis (ACD), a chronic inflammatory skin disease, is a type IV delayedhypersensitivity response induced by sensitization to allergens that causes redness, edema, and dryness of the skin [1,2]. The prevalence of ACD in children and adults worldwide is 15–20% and 1–3%, respectively [3,4,5]. The prevalence rate of ACD is higher in young children under 10 years than it is adults [3,6]. Systemic corticosteroid or steroids combined with methotrexate, and azathioprine have been used for ACD [7]. There is a need to develop novel agents, preferably from natural products, to treat ACD [3]

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