Pediococcus pentosaceus-Fermented Cordyceps militaris Inhibits Inflammatory Reactions and Alleviates Contact Dermatitis

Int J Mol Sci. 2018 Nov 7;19(11):3504. doi: 10.3390/ijms19113504.

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.

Keywords: DNFB-induced ACD mice; GRC-ON89A; NF-κB; anti-inflammatory; macrophage.

MeSH terms

  • Adenosine / analysis
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cordyceps / chemistry*
  • Deoxyadenosines / analysis
  • Dermatitis, Contact / complications
  • Dermatitis, Contact / drug therapy*
  • Dermatitis, Contact / pathology
  • Down-Regulation
  • Fermentation*
  • Flavonoids / analysis
  • I-kappa B Proteins / metabolism
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Pediococcus pentosaceus / metabolism*
  • Phosphorylation / drug effects
  • Polyphenols / analysis
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Deoxyadenosines
  • Flavonoids
  • I-kappa B Proteins
  • Inflammation Mediators
  • Interleukin-1beta
  • Lipopolysaccharides
  • Polyphenols
  • RNA, Messenger
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Mitogen-Activated Protein Kinases
  • cordycepin
  • Adenosine