title: Anti-inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression.
abstract: OBJECTIVE
  In this study, we investigated the regulatory effects of honokiol on various inflammatory events mediated by monocytes/macrophages (U937/RAW264.7 cells) and lymphocytes (splenic lymphocytes and CTLL-2 cells) and their putative action mechanism.
  
  
  METHODS
  In order to investigate the regulatory effects, various cell lines and primary cells (U937, RAW264.7, CTLL-2 cells, and splenic lymphocytes) were employed and various inflammatory events, such as the production of inflammatory mediators, cell adhesion, cell proliferation, and the early signaling cascade, were chosen.
  
  
  RESULTS
  Honokiol strongly inhibited various inflammatory responses, such as: (i) the upregulation of nitric oxide (NO), prostaglandin E2 and TNF-alpha production and costimulatory molecule CD80 induced by lipopolysaccharide (LPS); (ii) the functional activation of beta1-integrin (CD29) assessed by U937 cell-cell and cell-fibronectin adhesions; (iii) the enhancement of lymphocytes and CD8+CTLL-2 cell proliferation stimulated by LPS, phytohemaglutinin A (PHA), and concanavalin A or interleukin (IL)-2; and (iv) the transcriptional upregulation of inducible NO synthase, TNF-alpha, cyclooxygenase-2, IL-12, and monocyte chemoattractant protein (MCP)-1. These anti-inflammatory effects of honokiol seem to be mediated by interrupting the early activated intracellular signaling molecule phosphoinositide 3-kinase (PI3K)/Akt, but not Src, the extracellular signal-regulated kinase, and p38, according to pharmacological, biochemical, and functional analyses.
  
  
  CONCLUSIONS
  These results suggest that honokiol may act as a potent anti-inflammatory agent with multipotential activities due to an inhibitory effect on the PI3K/Akt pathway.
authors.affiliation: School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
authors.forename: Byung Hun
authors.initials: BH
authors.lastname: Kim
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D015232:Dinoprostone; D005353:Fibronectins; D017705:Lignans; D008070:Lipopolysaccharides; D008934:Mitogens; D009569:Nitric Oxide; D051058:Oncogene Protein v-akt; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C022616:thiazolyl blue