title: Synergistic anti-inflammatory effects of nobiletin and sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells.
abstract: Inflammation plays important roles in the initiation and progress of many diseases including cancers in multiple organ sites. Herein, we investigated the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN), in combination. Noncytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that combined NBN and SFN treatments produced much stronger inhibitory effects on the production of nitric oxide (NO) than NBN or SFN alone at higher concentrations. These enhanced inhibitory effects were synergistic based on the isobologram analysis. Western blot analysis showed that combined NBN and SFN treatments synergistically decreased iNOS and COX-2 protein expression levels and induced heme oxygenase-1 (HO-1) protein expression. Real-time polymerase chain reaction analysis indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels and synergistically increased HO-1 mRNA levels. Overall, our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells.
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, Shandong, People's Republic of China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Guo
authors.forename: Peiju
authors.initials: P
authors.lastname: Qiu
authors.forename: Guang
authors.initials: G
authors.lastname: Xu
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.forename: Guanpin
authors.initials: G
authors.lastname: Yang
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.forename: David Julian
authors.initials: DJ
authors.lastname: McClements
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D047309:Flavones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000235:genetics; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D017879:Isothiocyanates; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D047309:Flavones; D007375:Interleukin-1; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D013454:Sulfoxides; D013861:Thiocyanates; D009569:Nitric Oxide; C008661:nobiletin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C016766:sulforaphane