title: Specific oligopeptides in fermented soybean extract inhibit NF-κB-dependent iNOS and cytokine induction by toll-like receptor ligands.
abstract: The ethanol extract of fermented soybean from Glycine max (chungkookjang, CHU) has been claimed to have chemopreventive and cytoprotective effects. In the present study, we examined the inhibitory effect of CHU on inducible nitric oxide synthase (iNOS) and cytokine induction by toll-like receptor (TLR) ligands treatment and attempted to identify the responsible active components. Nitric oxide (NO) content and iNOS levels in the media or RAW264.7 cells were measured using the Griess reagent and real-time polymerase chain reaction assays. CHU treatment inhibited NO production and iNOS induction elicited by lipopolysaccharide (LPS, TLR4L) in a concentration-dependent manner. Tumor necrosis factor-α and interleukin-6 productions were also diminished. Peptidoglycans (TLR2/6L) and CpG-oligodeoxynucleotides (TLR9L) from CHU inhibited iNOS induction, but not poly I:C (TLR3L) or loxoribine (TLF7L). The anti-inflammatory effect resulted from the inhibition of nuclear factor-kappa B (NF-κB) through the inhibition of inhibitory-κB degradation. Of the representative components in CHU, specific oligopeptides (AFPG and GVAWWMY) had the ability to inhibit iNOS induction by LPS, whereas others failed to do so. Daidzein, an isoflavone used for comparative purposes, was active at a relatively higher concentration. In an animal model, oral administration of CHU to rats significantly diminished carrageenan-induced paw edema and iNOS induction. Our results demonstrate that CHU has anti-inflammatory effects against TLR ligands by inhibiting NF-κB activation, which may result from specific oligopeptide components in CHU. Since CHU is orally effective, dietary applications of CHU and/or the identified oligopeptides may be of use in the prevention of inflammatory diseases.
authors.affiliation: 1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Korea.
authors.forename: Woo Hyung
authors.initials: WH
authors.lastname: Lee
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Wu
authors.forename: Chan Gyu
authors.initials: CG
authors.lastname: Lee
authors.forename: Dae Il
authors.initials: DI
authors.lastname: Sung
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Song
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kim
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan; D016207:Cytokines / Q000378:metabolism*; D004032:Diet; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D005285:Fermentation; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D010457:Peptidoglycan / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D012639:Seeds / Q000737:chemistry / Q000382:microbiology; D013025:Glycine max / Q000737:chemistry* / Q000382:microbiology; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D010457:Peptidoglycan; D010936:Plant Extracts; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II
keywords: chungkookjang; food supplement; inflammation