title: Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation.
abstract: BACKGROUND
  More than 50% of sepsis cases are caused by Streptococcus pneumoniae, and hospital mortality related to sepsis comprises 52% of all hospital deaths. Therefore, sepsis is a medical emergency, and any treatment against the agent that produces it, is welcome.
  
  
  OBJECTIVE
  The role of Panax ginseng C.A. Meyer (Araliaceae) aqueous extract in bacterial infection in vivo is not well understood. Here, the protective effect of Korean red ginseng (KRG) extract against pneumococcal infection and sepsis was elucidated.
  
  
  METHODS
  In this study, mice were administrated KRG (25, 50, 100 mg/kg) for 15 days, and then infected with a lethal S. pneumoniae strain. Survival rate, body weight, and colonization were determined.
  
  
  METHODS
  The RAW 264.7 macrophage cells were infected with S. pneumoniae and cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inflammation was examined using an enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (HE) staining while gene expression was determined using western blotting.
  
  
  RESULTS
  KRG-pre-treated mice (100 mg/kg of KRG) had significantly higher survival rates and body weights than those of the non-treated controls; KRG-pre-treated mice had lower bacterial number and morbidity than those of the non-treated controls. 100 mg/kg of KRG administration decreased cytokine levels including tumor necrosis factor (TNF)-α (897 and 623 pg/ml, control and KRG groups, respectively, P < 0.05) and interleukin (IL)-1β (175 and 127 pg/ml, control and KRG groups, respectively, P = 0.051), nitric oxide level (149 and 81 nM, control and KRG groups, respectively, P < 0.05), and neutrophil infiltration 48 h post-infection, in vivo. In pneumococcal infection, KRG pre-treatment downregulated toll-like receptor (TLR) 4 and TNF-ɑ expressions in RAW 264.7 macrophage cells and increased cell survival by activating phosphoinositide 3-kinase (PI3K)/AKT signaling.
  
  
  CONCLUSIONS
  Taken together, 100 mg/kg of KRG appeared to protect host cells from lethal pneumococcal sepsis by inhibiting inflammation as well as by enhancing bacterial clearance thereby reinforcing cell survival against pneumococcal infection.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Cuong Thach
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Truc Thanh
authors.initials: TT
authors.lastname: Luong
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seung Yeop
authors.initials: SY
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Gyu Lee
authors.initials: GL
authors.lastname: Kim
authors.affiliation: Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Asan 336-745, Republic of Korea.
authors.forename: Hyogyoung
authors.initials: H
authors.lastname: Kwon
authors.affiliation: The Korean Ginseng Research Institute, Korea Ginseng Co., Daejeon 305-805, Republic of Korea.
authors.forename: Hong-Gyun
authors.initials: HG
authors.lastname: Lee
authors.affiliation: The Korean Ginseng Research Institute, Korea Ginseng Co., Daejeon 305-805, Republic of Korea.
authors.forename: Chae-Kyu
authors.initials: CK
authors.lastname: Park
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: dkrhee@skku.edu.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D005894:Panax / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy*; D000067996:RAW 264.7 Cells; D018805:Sepsis / Q000188:drug therapy*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases
keywords: Korean red ginseng; Panax ginseng C.A. Meyer; Pneumococcus; Sepsis; Streptococcus pneumoniae; in vivo