title: The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis.
abstract: Despite recent advances in antibiotic therapy and intensive care, sepsis remains a widespread problem in critically ill patients. The high mortality from sepsis is in part mediated by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., tumor necrosis factor, interleukin-1, and interferon-gamma) and late [e.g., high mobility group box 1 protein (HMGB1)] proinflammatory cytokines. Our discovery of HMGB1 as a late mediator of lethal systemic inflammation has initiated a new field of investigation for the development of experimental therapeutics. A popular Chinese herb, Angelica sinensis (also known as Dang Gui or Dong Quai) has been used traditionally for treating women with gynecological disorders (such as dysmenorrheal and hot flashes). Here we examined the effect of Angelica sinensis extract on endotoxin-induced HMGB1 release in vitro, and explored its therapeutic potential in animal models of lethal endotoxemia and sepsis [induced by cecal ligation and puncture (CLP)] in vivo. We demonstrated that a low-molecular-weight (<10 kDa) fraction of A. sinensis extract significantly attenuated endotoxin-induced HMGB1 release in part through interfering with its cytoplasmic translocation in macrophage cultures. Prophylactic administration of an aqueous extract of A. sinensis significantly attenuated systemic HMGB1 accumulation in vivo, and conferred a dose-dependent protection against lethal endotoxemia. Furthermore, delayed administration of A. sinensis extract beginning 24 h after CLP attenuated systemic HMGB1 accumulation, and significantly rescued mice from lethal sepsis. Taken together, these data suggest that A. sinensis contains water-soluble components that exert protective effects against lethal endotoxemia and experimental sepsis in part by attenuating systemic accumulation of a late proinflammatory cytokine, HMGB1.
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY 11030, USA. hwang@nshs.edu
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rendon-Mitchell
authors.forename: Mahendar
authors.initials: M
authors.lastname: Ochani
authors.forename: Mala
authors.initials: M
authors.lastname: Ashok
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sama
mesh_terms: D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D019446:Endotoxemia / Q000178:diet therapy / Q000517:prevention & control*; D004731:Endotoxins / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D021381:Protein Transport; D018805:Sepsis / Q000178:diet therapy / Q000517:prevention & control*
chemical_list: D003373:Coumaric Acids; D004731:Endotoxins; D024243:HMGB1 Protein; D010936:Plant Extracts; C004999:ferulic acid