RESUMEN
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.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Factor 6 Asociado a Receptor de TNF/metabolismo , Ubiquitinación/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Animales , Citocinas/metabolismo , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular , Lipopolisacáridos , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Subunidad p50 de NF-kappa B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Emodina/uso terapéutico , Inflamación/tratamiento farmacológico , Activación de Macrófagos/efectos de los fármacos , Animales , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Inmunoglobulina E/metabolismo , Inflamación/patología , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Pulmón/patología , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/patologíaRESUMEN
Crude SHP was obtained from extracting with hot water and precipitating with ethyl alcohol. Free proteins were removed by trypsinase combined with Sevage method. Different fractions were got by gel filtration chromatography. The molecule structure was analyzed by ultraviolet spectrum scanning and KBr infrared spectroscope. The results showed that the reaction of phenol-sulfuric acid was postiive, reaction of ninhydrin was weak positive and reaction of iodine-potassium iodide was negative, the extraction was regarded as a non-starch polysaccharide. Extraction rate of SHP was 8.56% and the content of polysaccharides was 90.96%. Gel filtration chromatography showed that SHP composed of furanopolysaccharides, xylose, galactose, arabinose, glucose, rhamnose and fructose. Ultraviolet spectrum showed that SHP contained little DNA and protein, infrared spectrum showed that SHP was main furanopolysaccharides and had beta-glycosidic bouds in its molecule structure, and there was a characteristic absorb peak of at-D-galactopyranosyl in it.