title: A highly purified vegetal fraction able to modulate HMGB1 and to attenuate septic shock in mice.
abstract: High-mobility group box protein 1 (HMGB1) is an intracellular protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. Its inhibition in animal experiments, even in the late phase of septic shock, significantly enhanced the survival rate of rodents. The aim of our study was to investigate the effect of a vegetal fraction isolated and highly purified from Helleborus purpurascens regarding the modulation of HMGB1 release either from tumor cells or human blood mononuclear cells. Our results showed that the vegetal fraction was able to down-regulate the release of HMGB1 from activated human blood mononuclear cells (PBMCs) and tumor cells. By combining the purified fraction with Cyclophosphamide the release of HMGB1 from tumor cells was strongly decreased. This synergism was not noticed when the ve getal product was associated with Doxorubicin. We also studied the effect of the purified fraction in mice with septic shock induced by cecal ligation and puncture (CLP) method. The tested vegetal product increased significantly the survival rate of animals compared to the mice not treated with it. Our data suggest that the purified vegetal fraction may modulate inflammation by down-regulating the HMGB1, which can also explain its efficacy in septic shock in mice.
authors.affiliation: "Cantacuzino" National Institute of Research - Development in Microbiology and Immunology, Bucharest, Romania.
authors.forename: Natalia Simona
authors.initials: NS
authors.lastname: Apetrei
authors.forename: Ana
authors.initials: A
authors.lastname: Călugăru
authors.forename: F
authors.initials: F
authors.lastname: Kerek
authors.forename: Minerva
authors.initials: M
authors.lastname: Panteli
authors.forename: I
authors.initials: I
authors.lastname: Rasit
authors.forename: Lidia
authors.initials: L
authors.lastname: Cremer
authors.forename: G
authors.initials: G
authors.lastname: Szegli
authors.forename: Andreea-Roxana
authors.initials: AR
authors.lastname: Lupu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D039322:Helleborus / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy*
chemical_list: D024243:HMGB1 Protein; D010936:Plant Extracts