title: Nitric oxide production inhibition and mechanism of phenanthrene analogs in lipopolysaccharide-stimulated RAW264.7 macrophages.
abstract: Natural phenanthrene derivatives are considered to be important resource for the anti-inflammatory therapeutics, but their structure-activity relationship and mechanisms are still unknown. In this study we evaluated 20 synthesized phenanthrene analogs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 10, 11 and 17 were found to inhibit the production of nitric oxide (NO) with IC50 values of 37.26μM, 5.05μM and 20.31μM, respectively. Compound 11 decreased LPS-induced expression of inducible NO synthase (iNOS), inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK) and serine/threonine kinase Akt. It also suppressed the phosphorylation and degradation of inhibitory kappa B-α (IκBα). Data obtained suggest that compound 11 exerts anti-inflammatory effects by inhibiting p38 MAPK and nuclear factor κB (NF-κB) pathways, which warrants further investigation as a new anti-inflammatory pharmaceutical tool.
authors.affiliation: School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China; Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
authors.forename: Lian-Qi
authors.initials: LQ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Shen
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Hu
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria.
authors.forename: Ighodaro
authors.initials: I
authors.lastname: Igbe
authors.affiliation: College of Chemistry and Materials, Sichuan Normal University, Chengdu, China.
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, China. Electronic address: ymhpz@126.com.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China. Electronic address: wangfei@cib.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Anti-inflammatory activity; IκBα; Macrophage; Phenanthrene; p38