title: ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract.
abstract: BACKGROUND
  Korean Red Ginseng (KRG) is one of the representative traditional herbal medicines prepared from Panax ginseng Meyer (Araliaceae) in Korea. It has been reported that KRG exhibits a lot of different biological actions such as anti-aging, anti-fatigue, anti-stress, anti-atherosclerosis, anti-diabetic, anti-cancer, and anti-inflammatory activities. Although systematic studies have investigated how KRG is able to ameliorate various inflammatory diseases, its molecular inhibitory mechanisms had not been carried out prior to this study.
  
  
  METHODS
  In order to investigate these mechanisms, we evaluated the effects of a water extract of Korean Red Ginseng (KRG-WE) on the in vitro inflammatory responses of activated RAW264.7 cells, and on in vivo gastritis and peritonitis models by analyzing the activation events of inflammation-inducing transcription factors and their upstream kinases.
  
  
  RESULTS
  KRG-WE reduced the production of nitric oxide (NO), protected cells against NO-induced apoptosis, suppressed mRNA levels of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and interferon (IFN)-β, ameliorated EtOH/HCl-induced gastritis, and downregulated peritoneal exudate-derived NO production from lipopolysaccharide (LPS)-injected mice. The inhibition of these inflammatory responses by KRG-WE was regulated through the suppression of p38, c-Jun N-terminal kinase (JNK), and TANK-binding kinase 1 (TBK1) and by subsequent inhibition of activating transcription factor (ATF)-2, cAMP response element-binding protein (CREB), and IRF-3 activation. Of ginsensides included in this extract, interestingly, G-Rc showed the highest inhibitory potency on IRF-3-mediated luciferase activity.
  
  
  CONCLUSIONS
  These results strongly suggest that the anti-inflammatory activities of KRG-WE could be due to its inhibition of the p38/JNK/TBK1 activation pathway.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, Republic of Korea.
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hyunsik
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Ginseng Corporation Central Research Institute, Daejeon 305-805, Republic of Korea.
authors.forename: Yi-Seong
authors.initials: YS
authors.lastname: Kwak
authors.affiliation: Metabolic Engineering Division, National Academy of Agricultural Science, Rural Development Administration, Suwon 441-707, Republic of Korea.
authors.forename: Chang-Muk
authors.initials: CM
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jaecho@skku.edu.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D000431:Ethanol; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D005894:Panax; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D051698:Activating Transcription Factor 2; D000893:Anti-Inflammatory Agents; C497106:Atf2 protein, mouse; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D012997:Solvents; D018808:Transcription Factor AP-1; D014867:Water; D009569:Nitric Oxide; D000431:Ethanol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D006851:Hydrochloric Acid
keywords: ATF-2; Anti-inflammatory activity; CREB; IRF-3; Korean red ginseng; Panax ginseng Meyer