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1.
Membranes (Basel) ; 11(7)2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34357161

RESUMEN

BACKGROUND: The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. METHODS: The effects of the blockers inhalation on the reactivity of guinea pig airways, number of citric-acid-induced coughs and ciliary beating frequency (CBF) were tested in vivo. Chronic inflammation simulating asthma was induced by repetitive exposure to ovalbumin. The expression of Nav1.7 and Nav1.8 was examined by ELISA. RESULTS: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The Nav1.7 blockers significantly inhibited coughing and participated in CBF control in the ovalbumin-sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. The therapeutic potency of the Nav1.8 blocker was evidenced in combinations with classic bronchodilators. CONCLUSION: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker's compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. However, the influence of the Nav1.8 blocker on CBF requires further investigation.

2.
Eur J Pharmacol ; 891: 173698, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33129789

RESUMEN

Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-ß1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-ß1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).


Asunto(s)
Antiasmáticos/farmacología , Broncoconstricción/efectos de los fármacos , Quempferoles/farmacología , Pulmón/efectos de los fármacos , Neumonía/prevención & control , Hipersensibilidad Respiratoria/prevención & control , Tráquea/efectos de los fármacos , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Líquido del Lavado Bronquioalveolar/química , Tos/inducido químicamente , Tos/metabolismo , Tos/fisiopatología , Tos/prevención & control , Citocinas/metabolismo , Modelos Animales de Enfermedad , Cobayas , Mediadores de Inflamación/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Pulmón/metabolismo , Pulmón/fisiopatología , Masculino , Ovalbúmina , Neumonía/inducido químicamente , Neumonía/metabolismo , Neumonía/fisiopatología , Hipersensibilidad Respiratoria/inducido químicamente , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/fisiopatología , Tráquea/metabolismo , Tráquea/fisiopatología , Factor de Crecimiento Transformador beta1/metabolismo
3.
Int J Biol Macromol ; 165(Pt A): 842-848, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33022347

RESUMEN

Many native plant biopolymers or derivatives thereof have interesting biological effects and therefore the search for additional biological activities is important to map their overall effects. A low molecular weight (Mw = 7600 g/mol) hemicellulose polymer α-L-arabino(4-O-methyl-α-D-glucurono)-ß-D-xylan (AGX) was isolated from the crushed roots of the Rudbeckia fulgida medicinal plant by alkaline extractions and anion-exchange chromatography. Analysis of neutral sugars revealed a predominance of xylose (82.3 wt%) and arabinose (6.8 wt%), while other neutral sugars were found only in small amounts as contaminants. The uronic acid content in Rudbeckia AGX was determined to be 8.8 wt%. Pharmacological tests showed that Rudbeckia AGX effectively suppressed cough and the initial amplitude of histamine/methacholine-induced bronchoconstriction in healthy OVA-sensitive guinea pigs. In addition, its effect at a dose of 100 mg/kg was similar to or greater than that of the positive control bronchodilator salbutamol and the antitussive codeine agent. These findings support the fact that Rudbeckia AGX could be a suitable candidate for alternative treatment of allergic asthma.


Asunto(s)
Antiasmáticos , Asma/tratamiento farmacológico , Raíces de Plantas/química , Rudbeckia/química , Xilanos , Animales , Antiasmáticos/química , Antiasmáticos/aislamiento & purificación , Antiasmáticos/farmacología , Asma/metabolismo , Asma/patología , Secuencia de Carbohidratos , Modelos Animales de Enfermedad , Cobayas , Humanos , Masculino , Xilanos/química , Xilanos/aislamiento & purificación , Xilanos/farmacología
4.
Int J Biol Macromol ; 162: 188-198, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32565301

RESUMEN

Microalgal exopolysaccharides (EPSs) are given great attention due to their potential biotechnology applications. Purified C. vulgaris EPS was subjected to compositional and sugar linkage analyses, and partial acid hydrolysis. Hydrolysate separation by gel chromatography afforded oligosaccharide fractions. Both, EPS and oligomers were studied by NMR spectroscopy. Data suggest very complex highly branched α-L-arabino-α-L-rhamno-α,ß-D-galactan structure. Backbone repeating unit is formed by →2)-α-L-Rha (1 â†’ 3)-α-L-Rha(1 â†’ sequence, highly branched by long 1,6-linked α-D-Galp side chains, further branched at C2, C3 or C4 by α-L-Araf, α-D-Galf and ß-D-Galf residues. α-L-Araf form longer 1,2-linked chains branched at C3, C4 or C5. Galf residues are localized as terminal units predominantly in the ß configuration, while α-D-Galp and α-L-Araf may be partially O-methylated. Ex vivo biological assays showed increased interleukin-12 (IL-12) and interferon-gamma (INF-γ) levels corresponding to transforming growth factor beta (TGF-ß) decrease in guinea pig model experimental asthma. These facts point to the anti-remodelling effect of Chlorella EPS and suggest its possible application in the treatment of asthma and chronic obstructive pulmonary disorder.


Asunto(s)
Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Chlorella vulgaris/química , Galactanos/química , Galactanos/uso terapéutico , Oligosacáridos/análisis , Oligosacáridos/uso terapéutico , Animales , Asma/inducido químicamente , Budesonida/uso terapéutico , Cromatografía en Gel , Modelos Animales de Enfermedad , Cobayas , Hidrólisis , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Espectroscopía de Resonancia Magnética , Oligosacáridos/química , Ovalbúmina/toxicidad , Factor de Crecimiento Transformador beta/metabolismo
5.
Int J Biol Macromol ; 160: 364-371, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32442574

RESUMEN

Complex structure of cyanobacterium Nostoc sp. exopolysaccharide (EPS), with apparent molecular weight 214 × 103 g/mol, can be deduced from its composition. Chemical and NMR analyses found four dominant sugar monomers, namely (1 → 4)-linked α-l-arabinopyranose, ß-d-glucopyranose, ß-d-xylopyranose and (1 → 3)-linked ß-d-mannopyranose, two different uronic acids and a lactyl group, with (1 → 4,6)-linked ß-d-glucopyranose as the only branch point suggest a complex structure of this polymer. The dominant uronic acid is α-linked, but it remained unidentified. ß-d-Glucuronic acid was present in lower amount. Their position as well as that of lactyl remained undetermined too. Different doses of orally administered EPS in guinea pigs evoked a significant decrease in cough effort and a decrease in airway reactivity. The antitussive efficacy and bronchodilator effect of higher doses of EPS were found to be similar to that of the antitussive drug codeine and the antiasthmatic salbutamol. Without significant cytotoxicity on the RAW 264.7 cells, EPS stimulated the macrophage cells to produce pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and prostaglandins (PGs) and nitric oxide (NO) via induction of COX-2 and iNOS expression, respectively, suggesting that this biopolymer potentiates an early innate immune response and can therefore be used as a new immune modulator.


Asunto(s)
Cianobacterias/metabolismo , Nostoc/metabolismo , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/farmacología , Albuterol/farmacología , Animales , Biopolímeros/química , Broncodilatadores/farmacología , Línea Celular , Codeína/farmacología , Tos/tratamiento farmacológico , Citocinas/metabolismo , Ácido Glucurónico/química , Cobayas , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismo , Ácidos Urónicos/química
6.
Int J Biol Macromol ; 135: 1-11, 2019 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-31121228

RESUMEN

Microalgae are the lowest plant organisms producing a wide range of metabolites that make them interesting organisms for industrial applications. Cultivation of green microalgal species Chlorella vulgaris resulted a significant production of extracellular polysaccharide (EPS). Preliminary chemico-spectroscopic studies on EPS revealed its molecular profile, a complex primary structure consisting of six monosaccharide units occurring in both furano and pyrano forms, a high sugar binding variability and the presence of partially methylated derivatives of some sugar constituents. Biological activity tests showed that EPS caused significant bronchodilatory, anti-inflammatory and antitussive effects in test animals. Chlorella EPS appears to be a promising agent for the prevention of chronic airway inflammation, which is the basic pathogenic mechanism of many respiratory diseases, including bronchial asthma.


Asunto(s)
Antiasmáticos/química , Antiasmáticos/farmacología , Chlorella vulgaris/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Alérgenos , Animales , Antiasmáticos/metabolismo , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Fenómenos Químicos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Espacio Extracelular/metabolismo , Cobayas , Mediadores de Inflamación/metabolismo , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/inmunología , Músculo Liso/metabolismo , Polisacáridos/biosíntesis , Análisis Espectral
7.
Carbohydr Polym ; 198: 215-224, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30092993

RESUMEN

Microalgae occupy all territories and their products represent a rich source of phytochemicals for human being. Green microalga Dictyosphaerium chlorelloides was found to be a significant producer of the extracellular biopolymer. Dominant components of the biopolymer were found to be Gal (39 wt%) with its methyl derivatives (15 wt%), Rha (19 wt%) and Man (14 wt%). 2-OMe-Gal was found to be the major derivative while other sugars, namely 3-OMe-, 6-OMe- and 2,3-di-OMe-Gal, 3-OMe-Glc and 4-OMe-Xyl were in smaller amounts. NMR spectroscopy revealed complex structure with galactan backbone branched by sugars in furano and pyrano forms in alpha and beta configurations. NMR data of 2-OMe, 3-OMe, 2,3-OMe and 6-OMe galactoses afforded characteristic values for O-methyls in each position. Biopolymer antitussive effect was similar to that of centrally acting antitussive drugs, indicating its relatively good antitussive potential.


Asunto(s)
Biopolímeros/análisis , Chlorophyta/metabolismo , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Antitusígenos/farmacología , Biopolímeros/química , Biopolímeros/metabolismo , Biopolímeros/farmacología , Tos/tratamiento farmacológico , Cobayas , Espectroscopía de Resonancia Magnética , Masculino , Peso Molecular
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