ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract

J Ethnopharmacol. 2014 May 28;154(1):218-28. doi: 10.1016/j.jep.2014.04.008. Epub 2014 Apr 13.

Abstract

Ethnopharmacological relevance: 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.

Materials and 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.

Conclusion: 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.

Keywords: ATF-2; Anti-inflammatory activity; CREB; IRF-3; Korean red ginseng; Panax ginseng Meyer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Line
  • Cell Survival / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cytokines / genetics
  • Ethanol
  • Gastritis / chemically induced
  • Gastritis / drug therapy
  • Gastritis / metabolism
  • HEK293 Cells
  • Humans
  • Hydrochloric Acid
  • Interferon Regulatory Factor-3 / metabolism*
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Panax*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy
  • Peritonitis / metabolism
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • RNA, Messenger / metabolism
  • Solvents / chemistry
  • Transcription Factor AP-1 / metabolism
  • Water / chemistry

Substances

  • Activating Transcription Factor 2
  • Anti-Inflammatory Agents
  • Atf2 protein, mouse
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • RNA, Messenger
  • Solvents
  • Transcription Factor AP-1
  • Water
  • Nitric Oxide
  • Ethanol
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Hydrochloric Acid