title: Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor-κB in LPS-stimulated RAW264.7 cells.
abstract: Herbacetin (3,4',5,7,8-pentahydroxyflavone), an active flavonol compound within flavonoid, has been shown to induce apoptosis in HepG2 cells and suppress hepatocyte growth factor-induced motility of human breast cancer MDA-MB-231 cells. However, the anti-inflammatory mechanisms of Herbacetin have not been researched. In this study, we examined the inflammatory responses stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophage cells after pretreatment with different concentrations of Herbacetin. We found that Herbacetin decreased nitric oxide (NO) production in LPS-induced RAW264.7 and mouse bone marrow-derived macrophages. In addition, Herbacetin inhibited the LPS-induced expression of inducible nitric oxide synthase mRNA and protein in RAW264.7 cells. Treatment with Herbacetin decreased the release of proinflammatory cytokines, including TNF-α and IL-1β. Moreover, Herbacetin inhibited the activity of JNK kinase and nuclear factor-κB, signaling molecules involved in NO production. Cell signaling analysis using Bay 11-7082 (an inhibitory κB kinase 2 inhibitor) and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 for p38, SP600125 for JNK, and PD 98059 for ERK) suggested that LPS induced iNOS expression via activation of the JNK and NF-κB pathway, but not the p38 and ERK pathway. These findings suggest that Herbacetin exerts an anti-inflammatory effect through suppression of LPS-induced JNK and NF-κB signaling pathways and diminished production of proinflammatory cytokines and mediators.
authors: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors: Liang
authors: L
authors: Li
authors: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors: Mahesh
authors: M
authors: Sapkota
authors: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors: Se-woong
authors: SW
authors: Kim
authors: Department of Dental Pharmacology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: ysoh@jbnu.ac.kr.
authors: Yunjo
authors: Y
authors: Soh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; C581534:herbacetin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Anti-inflammation; Herbacetin; Inducible nitric oxide synthase; MAPK; NF-κB