title: Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice.
abstract: 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.
  
  
  
  This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG) is a good strategy to reduce intestinal inflammation.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Radiobiology and Human Health, ENEA, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Vitali
authors.forename: Francesca
authors.initials: F
authors.lastname: Palone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.forename: Anna
authors.initials: A
authors.lastname: Negroni
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cavone
authors.forename: Manuela
authors.initials: M
authors.lastname: Costanzo
authors.forename: Marina
authors.initials: M
authors.lastname: Aloi
authors.forename: Anna
authors.initials: A
authors.lastname: Dilillo
authors.forename: Laura
authors.initials: L
authors.lastname: Stronati
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D018836:Inflammation Mediators; D019695:Glycyrrhizic Acid