ABSTRACT
Isoalantolactone (IAL) is a sesquiterpene lactone extracted from roots of Inula helenium L and has shown anti-inflammatory effects. In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1ß, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 µM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K63-linked polyubiquitination of TRAF6, an upstream transcription factor of NF-κB, contributed to the anti-inflammatory effects of IAL. ALI was induced in mice by intratracheal injection of LPS (5 mg/kg). Administration of IAL (20 mg/kg, i.p.) significantly suppressed pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression. Our results demonstrate that IAL is a potential therapeutic reagent against inflammation and ALI.
Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Sesquiterpenes/therapeutic use , TNF Receptor-Associated Factor 6/metabolism , Ubiquitination/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Cytokines/metabolism , HEK293 Cells , Humans , Intracellular Signaling Peptides and Proteins , Lipopolysaccharides , Lung/pathology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , NF-kappa B p50 Subunit/metabolism , Signal Transduction/drug effectsABSTRACT
A Rh(III)-catalyzed one-pot reaction of N-phenoxyacetamides, ketones, and hydrazines for a facile access to disubstituted and trisubstituted ethylenes is reported. In this method, various ketones are transformed into donor-donor diazo compounds, which engage in insertion with N-phenoxyacetamides, following ß-H elimination under Rh(III) catalysis to generate (E)-polyaryl-substituted olefins. This chemistry features simple starting materials, mild reaction conditions, and good functional group tolerance.
ABSTRACT
Alternatively activated macrophages (AAMs) are not only associated with asthma but also lead to asthmatic airway inflammation and remodeling. Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. In this study we investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone), isolated from the rhizome of Rheum palmatum, alleviated asthmatic airway inflammation and reduced AAM polarization in a murine asthma model. Mice were sensitized with a triple allergen mix containing dust mite, ragweed and aspergillus (DRA). In mice with DRA-induced asthma, asthmatic inflammation was significantly enhanced. Intraperitoneal injection of emodin (20 mg·kg-1·d-1, ip) 1 h prior to DRA challenge on days 12-14 significantly decreased pulmonary eosinophil and lymphocyte infiltration, mucus secretion and serum IgE production, as well as IL-4 and IL-5 production in bronchoalveolar lavage fluid. In response to emodin treatment, activated markers of AAM Ym-1, Fizz-1 and arginase-1 in the lung tissues were remarkably decreased. In mouse bone marrow-derived macrophages (BMDMs) in vitro, emodin (2-50 µmol/L) dose-dependently inhibited IL-4-induced AAM polarization and STAT6 phosphorylation. Collectively, our results suggest that emodin effectively ameliorates asthmatic airway inflammation and AAM polarization, and it may therefore become a potential agent for the treatment of asthma.
Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Emodin/therapeutic use , Inflammation/drug therapy , Macrophage Activation/drug effects , Animals , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Immunoglobulin E/metabolism , Inflammation/pathology , Interleukin-4/metabolism , Interleukin-5/metabolism , Lung/pathology , Macrophages/metabolism , Male , Mice, Inbred C57BL , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/pathologyABSTRACT
The title compound, [Co(C11H8O5)(C8H7N3)] n , which is based on (E)-3-[3-(carb-oxy-meth-oxy)phen-yl]acrylic acid (H2L) and 3-(pyridin-4-yl)pyrazole (pp) ligands, has been synthesized under solvothermal conditions. The dihedral angle between pyrazole and pyridine rings in the pp ligands is 23.1â (2)°. In the crystal, helical chains formed by pp and L ligands connected to the CoII atom propagate parallel to the c axis. CoII atoms of adjacent chains are bridged by the acrylic acid groups of L ligands into corrugated polymeric sheets in the ac plane.
