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...
