Dataset Information

Penta-O-galloyl-?-D-glucose ameliorates inflammation by inhibiting MyD88/NF-?B and MyD88/MAPK signalling pathways.

ABSTRACT:

Background and purpose

The gallnut of Rhus chinensis?MILL and its main constituent penta-O-galloyl-?-D-glucose (PGG) inhibited NF-?B activation in LPS-stimulated peritoneal and colonic macrophages. Here we have investigated PGG mechanisms underlying anti-inflammatory effects of PGG in vitro and in vivo.

Experimental approach

Male C57BL/6 mice (18-22?g, 6 weeks old) were used to prepare peritoneal and colonic macrophages and for the induction of colitis by intrarectal administration of 2,3,4-trinitrobenzene sulphonic acid (TNBS). A range of inflammatory markers and transcription factors were evaluated by elisa, immunoblotting, flow cytometry and confocal microscopy.

Key results

Expression of Toll-like receptor (TLR)-4 or Lipopolysaccharide (LPS) binding to TLR-4 in LPS-stimulated peritoneal macrophages was not affected by PGG. However PGG inhibited binding of an anti-MyD88 antibody to peritoneal macrophages, but did not reduce binding of anti-IL-1 receptor-associated kinase (IRAK1) and IRAK4 antibodies to the macrophages with or without transfection with MyD88 siRNA. PGG potently reduced the activation of IRAK1, NF-?B, and MAPKs in LPS- or pepetidoglycan-stimulated peritoneal and colonic macrophages. PGG suppressed IL-1?, TNF-? and IL-6 in LPS-stimulated peritoneal macrophages, while increasing expression of the anti-inflammatorycytokine IL-10. Oral administration of PGG inhibited colon shortening and myeloperoxidase activity in mice with TNBS-induced colitis, along with reducing NF-?B activation and IL-1?, TNF-?, and IL-6 levels, whereas it increased IL-10.

Conclusions and implications

PGG reduced activation of NF-?B and MAPK signalling pathways by directly interacting with the MyD88 adaptor protein. PGG may ameliorate inflammatory diseases such as colitis.

SUBMITTER: Jang SE

PROVIDER: S-EPMC3949655 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Penta-O-galloyl-β-D-glucose ameliorates inflammation by inhibiting MyD88/NF-κB and MyD88/MAPK signalling pathways.

Jang Se-Eun SE Hyam Supriya R SR Jeong Jin-Ju JJ Han Myung Joo MJ Kim Dong-Hyun DH

British journal of pharmacology 20131101 5

<h4>Background and purpose</h4>The gallnut of Rhus chinensis MILL and its main constituent penta-O-galloyl-β-D-glucose (PGG) inhibited NF-κB activation in LPS-stimulated peritoneal and colonic macrophages. Here we have investigated PGG mechanisms underlying anti-inflammatory effects of PGG in vitro and in vivo.<h4>Experimental approach</h4>Male C57BL/6 mice (18-22 g, 6 weeks old) were used to prepare peritoneal and colonic macrophages and for the induction of colitis by intrarectal administratio ...[more]

PMID: 23941302

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