title: Sargaquinoic acid isolated from Sargassum siliquastrum inhibits lipopolysaccharide-induced nitric oxide production in macrophages via modulation of nuclear factor-κB and c-Jun N-terminal kinase pathways.
abstract: Nitric oxide (NO) is a crucial molecule in inflammatory diseases and is synthesized from L-arginine by a specific enzyme, NO synthase (NOS). The expression of inducible NOS (iNOS) is activated in macrophages by various stimuli, such as lipopolysaccharide (LPS), a wall component of gram-negative bacteria. LPS binds to toll-like receptor 4 (TLR4) on the macrophage surface and activates several downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways. This study investigated whether sargaquinoic acid isolated from Sargassum siliquastrum might have anti-inflammatory activity and interfere with NO production in macrophages by disrupting LPS-induced signaling. This study was conducted in vitro using RAW264.7 murine macrophages. LPS-stimulated cells were treated with sargaquinoic acid, and the effects on NO production, iNOS expression, and involvement of the NF-κB signaling pathway were investigated by Griess assay, western blotting, and confocal microscopy. The results demonstrated that sargaquinoic acid inhibited the production of NO and the expression of the iNOS protein in LPS-stimulated RAW264.7 macrophages. Moreover, sargaquinoic acid inhibited the degradation of inhibitory-κB protein (IκB)-α and the nuclear translocation of NF-κB, a key transcription factor for the regulation of iNOS expression. Also, sargaquinoic acid influenced the phosphorylation of JNK1/2 MAPK, except ERK1/2 and p38 MAPKs, stimulated by LPS. These results suggest that sargaquinoic acid specifically prevents NO production in macrophages via the blockade of NF-κB activation and may thus have therapeutic applications in various inflammatory diseases.
authors: Department of Pharmacology, School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors: Gyeoung-Jin
authors: GJ
authors: Kang
authors: Sang-Chul
authors: SC
authors: Han
authors: Weon-Jong
authors: WJ
authors: Yoon
authors: Young-Sang
authors: YS
authors: Koh
authors: Jin-Won
authors: JW
authors: Hyun
authors: Hee-Kyoung
authors: HK
authors: Kang
authors: Jae
authors: J
authors: Youl Cho
authors: Eun-Sook
authors: ES
authors: Yoo
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism; D044647:Sargassum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000475:Alkenes; D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C477718:sargaquinoic acid; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases