title: The molecular mechanism of polygalasaponin F-mediated decreases in TNFα: emphasizing the role of the TLR4-PI3K/AKT-NF-κB pathway.
abstract: Polygalasaponin F (PS-F), an oleanane-type triterpenoid saponin extracted from Polygala japonica, decreases the release of the inflammatory cytokine tumor necrosis factor α (TNFα), but the precise molecular mechanisms by which this event occurs are not fully understood. To study the anti-neuroinflammatory mechanisms of PS-F, enzyme-linked immunosorbent assay was used to detect the secretion of TNFα from BV-2 microglial cells. Nuclear proteins extracted from BV-2 microglial cells stimulated by lipopolysaccharide (LPS) and pretreated with/without inhibitors were measured by Western blotting, and cell viability was evaluated by MTT analysis. The results indicated that inhibition of toll-like receptor (TLR) 4 (CLI-095 1 μg/ml), phosphatidylinositol 3-kinase (PI3K) (Ly294002 10 μM) or IκBα phosphorylation (Bay11-7082 10 μM) completely prevents the release of TNFα induced by LPS without affecting cell viability and attenuated the nuclear translocation of p65 stimulated by LPS. In addition, PS-F exhibited a similar trend regarding TNFα release, AKT phosphorylation and NF-κB translocation. These results suggest that PS-F reduces neuroinflammatory cytokine secretion through the regulation of the TLR4-PI3K/AKT-NF-κB signaling pathway.
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050, China.
authors.forename: Wen-Fen
authors.initials: WF
authors.lastname: Yan
authors.forename: Qian-Hang
authors.initials: QH
authors.lastname: Shao
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Zhang
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides; D013450:Sulfones; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D012503:Saponins; D013449:Sulfonamides; D013450:Sulfones; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; C573752:polygalasaponin F; D019869:Phosphatidylinositol 3-Kinases
keywords: PI3K/AKT; TLR4; TNFα; polygalasaponin F