title: Chlorogenic acid attenuates high mobility group box 1 (HMGB1) and enhances host defense mechanisms in murine sepsis.
abstract: Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH₂-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors.forename: Chan-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002432:Cecum / Q000187:drug effects / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D024243:HMGB1 Protein / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology*; D007109:Immunity / Q000187:drug effects*; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008026:Ligation; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011677:Punctures; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018925:Chemokines; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1; D002726:Chlorogenic Acid