title: Cis- and Trans-gnetin H from Paeonia suffruticosa suppress inhibitor kappa B kinase phosphorylation in LPS-stimulated human THP-1 cells.
abstract: BACKGROUND
  The inflammatory response is an important mechanism in host defense; however, overstimulation and chronic inflammation are involved in many important human diseases. Currently, tumor necrosis factor-alpha blockers such as infliximab and adalimumab along with methotrexate are used in cases of severe and chronic disease. However, there are severe side effects and limitations associated with these treatments. Cis- and trans-gnetin H are compounds isolated from the seeds of Paeonia suffruticosa, a medicinal plant used in traditional Chinese medicine for the treatment of many conditions, including inflammatory diseases. In this study, we investigated possible anti-inflammatory mechanisms of cis- and trans-gnetin H against LPS-stimulated human THP-1 cells.
  
  
  METHODS
  PMA-differentiated THP-1 cells were pretreated with increasing concentrations of cis- and trans-gnetin H with or without LPS. Following treatment, cytotoxicity and the TNF-α, IL-1β, and IL-8 response were measured. We also characterized the nuclear translocation of NF-κB subunit p65 (RelA) by immunofluorescence and then investigated NF-κB activation by measuring the phosphorylation of NF-κB mediators, IKK-β, IκB α, and p65 by western blotting.
  
  
  RESULTS
  We found that cis- and trans-gnetin H significantly inhibited the cytokine response in a concentration-dependent manner without affecting cell viability. Cis- and trans-gnetin H effectively inhibited nuclear translocation of p65 and phosphorylation of IKK-β, IκB α, and p65. While both compounds showed promising anti-inflammatory effects, trans-gnetin H was determined to be more effective in suppressing cytokine responses.
  
  
  CONCLUSIONS
  We demonstrated that cis- and trans-gnetin H suppress cytokine response in LPS-stimulated THP-1 cells by preventing activation of key signaling molecules, IKK-β, IκB α, and p65, involved in the NF-κB pathway and suggest the use of cis- and trans-gnetin H in potential therapies for conditions and diseases associated with chronic inflammation.
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: hsp2g@mtmail.mtsu.edu.
authors.forename: Hyo S
authors.initials: HS
authors.lastname: Park
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: ejvick@gmail.com.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Vick
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: ying.gao@mtsu.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, No. 151 Malianwa, North Road, Haidian District, Beijing 100193, PR China. Electronic address: cnhe@implad.cn.
authors.forename: Chunnian
authors.initials: C
authors.lastname: He
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: nma2v@mtmail.mtsu.edu.
authors.forename: Nadin Marwan
authors.initials: NM
authors.lastname: Almosnid
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: mary.farone@mtsu.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Farone
authors.affiliation: Middle Tennessee State University, 1301 East Main Street, Murfreesboro, Tennessee 37132, USA. Electronic address: anthony.farone@mtsu.edu.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Farone
mesh_terms: D021581:Active Transport, Cell Nucleus; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D029596:Paeonia / Q000737:chemistry*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012118:Resorcinols / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; C498143:RELA protein, human; D012118:Resorcinols; D013267:Stilbenes; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C000596538:gnetin H; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammatory; Gnetin H; Inhibitor kappa B kinase; Nuclear translocation; Paeonia suffruticosa; Traditional Chinese medicine