Lavandulyl Flavonoids from Sophora flavescens Suppress Lipopolysaccharide-Induced Activation of Nuclear Factor-.KAPPA.B and Mitogen-Activated Protein Kinases in RAW264.7 Cells

Abstract

Oxidative stress, which is commonly defined as an imbalance between oxidants and antioxidants at the cellular level, has shown a deep interest constantly as the cause of cardiovascular events and a variety of vascular diseases. 1) One of the crucial steps in oxidative stress augmentation is the overproduction of reactive oxygen species (ROS).2) ROS encompass a variety of diverse chemical species including hydroxyl radical, nitric oxide (NO), and superoxide anion. In particular, the interaction between the superoxide anion and NO is important because it leads to the formation of the peroxynitrite. The peroxynitrite activates a variety of signaling pathways 3,4) and works deleteriously through its pro-atherosclerotic properties. 1)In general, NO and ROS are responsible for the regulation of the transcriptional pathways of nuclear factor-kB (NF-kB) that regulates expression of various inflammatory cytokines, chemokines, and adhesion molecules. 5) After activation by inflammatory cytokines and cellular stresses including tumor necrosis factor (TNF)-a and lipopolysaccharide (LPS), NF-kB proteins to translocate to the nucleus and bind their cognate DNA binding sites to regulate the transcription of a large number of genes including antimicrobial peptides, cytokines, chemokines, stress-response proteins, and antiapoptotic proteins.6) In addition to NF-kB, mitogen-activated protein kinases (MAPKs) have also been implicated in cytokine production in macrophages.7) Three MAPK families (extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK)) are signaling molecules that react to extracellular stimuli (mitogens) and regulate immune responses including proinflammatory cytokine production, mitosis, differentiation, and cell survival/apoptosis. 7,8)Sophora flavescens has long been traditionally used in asthma, bronchitis, bacterial, fungal infections, and skin disorders, and as an antipyretic, analgesic, anthelmintic, and remedy for stomach ailments.9) Lavandulylated (C 10 ) or prenylated (C 5 ) flavanones, lavandulyl chalcones, pterocarpanes, and quinolizidine alkaloids were isolated from S. flavescens. [10][11][12][13][14] They possess various biological activities such as anticancer, antioxidant, antibacterial, antifungal, antiviral, and anti-inflammatory activities. [15][16][17] Although the anti-inflammatory activities of flavonoids from S. flavesens have been reported, the mechanism of kurarinone (1), lavandulyl flavanone and kuraridin (2), lavandulyl chalcone on anti-inflammatory activity remains unclear in macrophages.In this study, we examined the effects of compounds 1 and 2 on LPS-mediated NO production, ROS generation, and expression of inflammatory cytokines, NF-kB activity, and phosphorylation of MAP kinases in murine RAW264.7 macrophages. MATERIALS AND METHODS General Experimental Materials and Cell CultureDulbecco's modified Eagle's medium (DMEM), fetal bovine serum (FBS), penicillin, and streptomycin were obtained from Cambrex (Verviers, Belgium). LPS was obtained from Sigma-Aldr...

Immunostimulating activity of maysin isolated from corn silk in murine RAW 264.7 macrophages

“…Han et al reported that flavonoids, kurarinone, and kuraridin affected iNOS and TNF-α production through MAPKs, including p38, ERK1/2 and JNK, and NF-κB activation, in RAW264.7 macrophages (22). Therefore, our results strongly suggested that maysin from CS induces TNF-α and iNOS production, through the NF-κB and Akt signaling pathways.…”

Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

“…[29][30][31] In addition, mitogen-activated protein kinases and NF-κB have been associated with the overproduction of these inflammatory mediators. 32 In previous studies, proinflammatory cytokines, such as TNF-α and IL-6, were completely blocked by hBD3 in pathogen-induced macrophages isolated from human bone marrow both in vitro and in vivo 33 through toll-like receptor-mediated signaling pathways and the subsequent transcriptional inhibition of inflammatory genes. 34 However, the therapeutic application of hBD3 has some limitations, including the difficulty of mass production due to its long amino acid sequence and the decreased stability observed at high ionic strength.…”

Comparative analysis of physicochemicals and antioxidative properties of new giant embryo mutant, YR23517Acp79, in rice (Oryza sativa L.)

“…To evaluate whether or not giant embryo (YR, KB) and normal embryo (IB) brown rice could inhibit LPS-induced NO generation in RAW 64.7 cells, we investigated NO production using Griess reaction assay. It is well known that LPS upregulates ROS and NO production through inducible nitric oxide synthase (iNOS) induction [Han et al, 2010]. As shown in Fig.…”