title: Pseuderanthemum palatiferum leaf extract inhibits the proinflammatory cytokines, TNF-α and IL-6 expression in LPS-activated macrophages.
abstract: The anti-inflammatory potential and underlying mechanisms of an ethanol extract of Pseuderanthemum palatiferum (EEP) leaves was investigated using LPS-activated macrophages. Our results show EEP produced a concentration-dependent suppression of TNF-α and IL-6 secretion by LPS-activated mouse peritoneal macrophages. EEP also suppressed LPS-induced TNF-α and IL-6 protein and mRNA levels in mouse-derived myeloid cell line RAW264.7. To further elucidate the molecular mechanisms responsible for impaired TNF-α and IL-6 regulation by EEP, the activation of transcription factors, NF-κB, C/EBP, and AP-1, was monitored using electrophoretic mobility shift assays. EEP suppressed LPS-induced NF-κB DNA binding activity within both the TNF-α and IL-6 promoters in RAW264.7 cells with impairment being more pronounced in the IL-6 promoter. In addition, EEP exhibited a concentration-dependent suppression of C/EBP and AP-1 DNA binding activity within the IL-6 promoter. Concordantly, IL-6 luciferase promoter reporter activity was also suppressed by EEP in transiently transfected RAW264.7 cells, upon LPS activation. EEP analysis by GC-MS and HPLC DAD-MSD revealed the presence of β-sitosterol and various polyphenols, respectively, which are known to possess anti-inflammatory activity. Collectively, these results suggest that the anti-inflammatory effects of EEP are mediated, at least in part, by modulating TNF-α and IL-6 expression through impairment of NF-κB, C/EBP, and AP-1 activity.
authors.affiliation: Division of Environmental Science, Faculty of Liberal Arts and Science, Sisaket Rajabhat University, Sisaket 33000, Thailand; School of Biology, Institute of Science, Suranaree University of Technology, NaKhon Ratchasima 30000, Thailand.
authors.forename: Patcharawan
authors.initials: P
authors.lastname: Sittisart
authors.affiliation: School of Pharmacology, Institute of Science, Suranaree University of Technology, NaKhon Ratchasima 30000, Thailand.
authors.forename: Benjamart
authors.initials: B
authors.lastname: Chitsomboon
authors.affiliation: Department of Pharmacology and Toxicology and Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA. Electronic address: kamins11@msu.edu.
authors.forename: Norbert E
authors.initials: NE
authors.lastname: Kaminski
mesh_terms: D027901:Acanthaceae / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D059808:Polyphenols / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors
keywords: AP-1; C/EBP; IL-6; NF-κB; Pseuderanthemum palatiferum; TNF-α