title: AKT-targeted anti-inflammatory activity of the methanol extract of Chrysanthemum indicum var. albescens.
abstract: BACKGROUND
  Wild chrysanthemum (Chrysanthemum indicum) is one of well-known medicinal plants traditionally used in Korea and China. As a variant of wild chrysanthemum, white wild chrysanthemum (Chrysanthemum indicum var. albescens) is also ethnopharmacologically applied to treat various symptoms such as inflammatory diseases.
  
  
  OBJECTIVE
  Although the anti-inflammatory activity of Chrysanthemum indicum has been reported, the anti-inflammatory activity and underlying molecular mechanism of white wild chrysanthemum are poorly understood.
  
  
  METHODS
  The effects of Chrysanthemum indicum var. albescens methanol extract (Civ-ME) on the production of inflammatory mediators, expression of pro-inflammatory genes, cell viability, and the activities of intracellular signaling molecules and transcription factors were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
  
  
  RESULTS
  Civ-ME suppressed the production of both nitric oxide (NO) and prostaglandin E2(PGE2) without cytotoxicity in LPS-stimulated RAW264.7 cells. Civ-ME was found to reduce the mRNA levels of inflammatory genes such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α and reduced NF-κB-mediated transcriptional activation. Civ-ME inhibited the nuclear translocation of NF-κB (p65 and p50), and its upstream signaling composed of IκBα and IKKα/β. An NF-κB luciferase reporter gene assay and an in vitro kinase assay confirmed that AKT1 and AKT2 might be direct pharmacological targets of Civ-ME. In addition, luteolin was identified by HPLC analysis as the main active pharmacological components of Civ-ME.
  
  
  CONCLUSIONS
  Civ-ME exerts an anti-inflammatory effect by targeting AKT1 and AKT2 in the NF-κB signaling pathway in macrophage-mediated inflammatory responses.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: real0902@gmail.com.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Heritage Material Research Team, Amorepacific R&D Unit, Yongin 446-729, Republic of Korea. Electronic address: dhkim417@amorepacific.com.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Republic of Korea. Electronic address: ysyi@cju.ac.kr.
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Yi
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: kjhmlkjhml@hanmail.net.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: you8755@nate.com.
authors.forename: Hye Yoon
authors.initials: HY
authors.lastname: Jeong
authors.affiliation: Heritage Material Research Team, Amorepacific R&D Unit, Yongin 446-729, Republic of Korea. Electronic address: khhwang@amorepacific.com.
authors.forename: Kyeonghwan
authors.initials: K
authors.lastname: Hwang
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic of Korea. Electronic address: jhkim1@chonbuk.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Heritage Material Research Team, Amorepacific R&D Unit, Yongin 446-729, Republic of Korea. Electronic address: superbody@amorepacific.com.
authors.forename: Junseong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: jaecho@skku.edu.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D031202:Chrysanthemum; D015232:Dinoprostone / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides; D000432:Methanol / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D012997:Solvents / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone; D000432:Methanol
keywords: AKT; Anti-inflammatory activity; Chrysanthemum indicum var. albescens; Macrophage; NF-κB