| Title | Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2013 |
| Authors | Vitali, Roberta, Palone Francesca, Cucchiara S., Negroni Anna, Cavone L., Costanzo Manuela, Aloi M., Dilillo A., and Stronati L. |
| Journal | PLoS ONE |
| Volume | 8 |
| Pagination | e66527 |
| ISSN | 19326203 |
| Keywords | advanced glycation end product receptor, animal, animal cell, animal experiment, animal model, animal tissue, Animalia, Animals, antagonists and inhibitors, antiinflammatory activity, antiinflammatory agent, article, autacoid, C57BL mouse, Cell Line, colitis, controlled study, cytokine, cytokine production, Cytokines, drug effect, Female, Gene expression, glycyrrhizate dipotassium, glycyrrhizic acid, high mobility group B protein, high mobility group B1 protein, HMGB1 Protein, human, human cell, Humans, in vitro study, in vivo study, Inbred C57BL, inflammation, Inflammation Mediators, interleukin 1beta, interleukin 6, intestine length, intestine parameters, messenger RNA, metabolism, Mice, mouse, Murinae, Mus, nonhuman, protein expression, protein secretion, real time polymerase chain reaction, Real-Time Polymerase Chain Reaction, toll like receptor 4, Tumor, tumor cell line, tumor necrosis factor alpha, unclassified drug, weight reduction |
| Abstract | Background:High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation.Aim:This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG) is a good strategy to reduce intestinal inflammation.Methods:Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS); a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses.Results:DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG.Conclusions:HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation. © 2013 Vitali et al. |
| Notes | cited By 17 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84879232713&doi=10.1371%2fjournal.pone.0066527&partnerID=40&md5=59932f0febdb020b5230241a27d1b502 |
| DOI | 10.1371/journal.pone.0066527 |
| Citation Key | Vitali2013 |
