title: 16α,17α-Epoxypregnenolone-20-oxime prevent LPS-induced NO production and iNOS expression in BV-2 microglial cells by inhibiting JNK phosphorylation.
abstract: The free radical nitric oxide (NO), a main member of neuroinflammatory cytokine and a gaseous molecule produced by activated microglia, has many physiological functions, including neuroinflammation. In the present study, we evaluated the effects of serial 16-dehydropregnenolone-3-acetate derivatives on lipopolysaccharide (LPS)-induced NO production and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells. Among the six derivatives tested, the increases in NO production and iNOS expression observed in BV-2 microglial cells after LPS stimulation were significantly inhibited by treatment with 16α, 17α-epoxypregnenolone-20-oxime. Moreover, the inhibitory effect of 16α,17α-epoxypregnenolone-20-oxime on NO production was similar to that of S-methylisothiourea sulfate (SMT), an iNOS inhibitor. Further studies showed that 16α,17α-epoxypregnenolone-20-oxime inhibited c-Jun N-terminal kinase (JNK) phosphorylation but not inhibitor kappa B (IκB)-α degradation. Our data in LPS-stimulated microglia cells suggest that 16α,17α-epoxypregnenolone-20-oxime might be a candidate therapeutic for treatment of NO induced neuroinflammation and could be a novel iNOS inhibitor.
authors.affiliation: College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University.
authors.forename: Hu-Nan
authors.initials: HN
authors.lastname: Sun
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Jin
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Han
authors.forename: Gui-Nan
authors.initials: GN
authors.lastname: Shen
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Yu
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Jin
authors.forename: Zheng-Xing
authors.initials: ZX
authors.lastname: Lian
authors.forename: Dong-Soek
authors.initials: DS
authors.lastname: Lee
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Ge
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Cui
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C000595300:16,17-epoxypregnenolone-20-oxime; D008070:Lipopolysaccharides; D010091:Oximes; D017382:Reactive Oxygen Species; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D011284:Pregnenolone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases