ABSTRACT
Aloe polysaccharides (APs) are acetyl polysaccharides. It has been reported APs could protect mice from ulcerative colitis (UC), but the complex interactions between APs and the intestinal barrier were unclear. Here, we investigated the relationship between APs and UC, and determined the synergistic effects of Nrf2/HO-1 signaling pathway and short-chain fatty acids (SCFAs) metabolism on protecting intestinal barrier in acute UC mice. Results showed APs could scavenge free radicals in vitro. In vivo, APs had the antioxidant and anti-inflammatory effect both in serum and colon. Besides, the pathological results showed APs could alleviate colonic lesions. Furthermore, our study indicated treatment with APs effectively increased SCFAs production. The inhibition of acute UC in mice was correlated with the APs-mediated effects on improving the expression of ZO-1, occludin, Nrf2, HO-I, and NQO1. Thus, APs effectively promoted the intestinal barrier via Nrf2/HO-1 signaling pathway and SCFAs metabolism, effectively ameliorating acute colitis in mice.
Subject(s)
Aloe/chemistry , Colitis, Ulcerative/drug therapy , Fatty Acids, Volatile/metabolism , Heme Oxygenase-1/metabolism , Membrane Proteins/metabolism , NF-E2-Related Factor 2/metabolism , Polysaccharides/administration & dosage , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/administration & dosage , Antioxidants/chemistry , Antioxidants/pharmacology , Carbohydrate Sequence , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Dextran Sulfate/chemical synthesis , Disease Models, Animal , Gene Expression Regulation/drug effects , Male , Mice , Polysaccharides/chemistry , Polysaccharides/pharmacology , Signal Transduction/drug effects , Treatment OutcomeABSTRACT
A novel water-dispersible conducting polymer analogous to poly(3,4-dioxythiophene):polystyrene sulfonate (PEDOT:PSS) has been chemically synthesized in a single reaction in high yield. PEDOT:DS, a new member of the polythiophene family, is composed of a complex between PEDOT and the sulfonated polysaccharide polyanion dextran sulfate. Drop-cast films of aqueous suspensions of the material display a native conductivity of up to 7 ± 1 S cm(-1), increasing to 20 ± 2 S cm(-1) after treatment with ethylene glycol and thermal annealing. Mass ratios of the precursors NaDS and EDOT were varied from 5:1 to 2:1 and a decrease in the NaDS:EDOT ratio produces tougher, less hygroscopic films of higher conductivity. Ultraviolet-visible spectroelectrochemistry yields spectra typical of PEDOT complexes. Cyclic voltammetry reveals that PEDOT:DS is electrochemically active from -1.0 to 0.8 V vs. Ag/Ag(+) in acetonitrile, with similar characteristics to PEDOT:PSS. Water dispersions of PEDOT:DS are successfully processed by drop casting, spray coating, inkjet printing and extrusion printing. Furthermore, laser etching of dried films allows the creation of patterns with excellent definition. To assess the cytotoxicity of PEDOT:DS, L-929 cells were cultured with a polymer complex concentration range of 0.002 to 0.2 g l(-1) in cell culture medium. No significant difference is found between the proliferation rates of L-929 cells exposed to PEDOT:DS and those in plain medium after 96h. However, PEDOT:PSS shows around 25% less cell growth after 4 days, even at the lowest concentration. Taken together, these results suggest PEDOT:DS has exceptional potential as an electromaterial for the biointerface.
Subject(s)
Biopolymers/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Dextran Sulfate/pharmacology , Electric Conductivity , Organic Chemicals/pharmacology , Polymers/pharmacology , Animals , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Cell Line , Cell Proliferation/drug effects , Dextran Sulfate/chemical synthesis , Dextran Sulfate/chemistry , Electrochemical Techniques , Mice , Microscopy, Electron, Scanning , Oxidation-Reduction , Particle Size , Polymers/chemical synthesis , Polymers/chemistry , Spectrum Analysis , TemperatureABSTRACT
A novel drug delivery system for the treatment of brain tumors was formulated by methotrexate (MTX)-loaded polymeric nanoparticles (NPs) based on Glycol chitosan (GCS) and Dextran sulfate (DS). The physicochemical properties of resulting particles were investigated, evidencing the contribution of these nanoparticles for brain targeting. In vitro release of MTX was also evaluated. The GCS-DS nanoparticles have been developed based on the modulation of ratio show promise as a system for controlled delivery of the drug to the brain.
Subject(s)
Brain Neoplasms/drug therapy , Chitosan/chemical synthesis , Dextran Sulfate/chemical synthesis , Nanoparticles/chemistry , Chitosan/chemistry , Drug Compounding , Hydrogen-Ion Concentration , Methotrexate/therapeutic use , Molecular Weight , Nanoparticles/ultrastructure , TemperatureABSTRACT
Multivalent neoglycoconjugates are valuable tools for studying carbohydrate-protein interactions. To study the interaction of HIV-1 gp120 with its reported alternate glycolipid receptors, galactosyl ceramide (GalCer) and sulfatide, galactose- and sulfated galactose-derivatized dendrimers were synthesized, analyzed as ligands for rgp120 by surface plasmon resonance, and tested for their ability to inhibit HIV-1 infection of CXCR4- and CCR5-expressing indicator cells. Four different series of glycodendrimers were made by amine coupling spacer-arm derivatized galactose residues, either sulfated or nonsulfated, to poly(propylenimine) dendrimers, generations 1-5. One series of glycodendrimers was prepared from the ceramide saccharide derivative of purified natural GalCer, and another was from chemically synthesized 3-(beta-D-galactopyranosylthio)propionic acid. Synthesis of 3-sulfogalactopyranosyl-derivatized dendrimers was accomplished using the novel compound, 3-(beta-D-3-sulfogalactopyranosylthio)propionic acid. The fourth series was made by random sulfation of the 3-(beta-D-galactopyranosylthio)propionic acid functionalized dendrimers. Structures of the carbohydrate moieties were confirmed by NMR, and the average molecular weights and polydispersities of the different glycodendrimers were determined using MALDI-TOF MS. Surface plasmon resonance studies found that rgp120 IIIB bound to the derivatized dendrimers tested with nanomolar affinity, and to dextran sulfate with picomolar affinity. In vitro studies of the effectiveness of these compounds at inhibiting infection of U373-MAGI-CCR5 cells by HIV-1 Ba-L indicated that the sulfated glycodendrimers were better inhibitors than the nonsulfated glycodendrimers, but not as effective as dextran sulfate.
Subject(s)
Glycoconjugates/chemical synthesis , Glycoconjugates/metabolism , HIV Envelope Protein gp120/metabolism , Receptors, Cell Surface/metabolism , Animals , Cattle , Dextran Sulfate/chemical synthesis , Dextran Sulfate/metabolism , Galactose/chemical synthesis , Galactose/metabolism , LigandsABSTRACT
Dextrans and pullulans of different molar masses in the range of 10(4)-10(5) g/mol were sulphated via a SO3-pyridine complex. The degree of substitution achieved was DS = 2.4 and DS = 1.4 for dextran sulphate and DS = 2.0 and DS = 1.4 for pullulan sulphate, respectively. Confirmation of sulphation was given by FTIR spectroscopy. Asymmetrical S=O and symmetrical C-O-S stretching vibrations were detected at 1260 and 820 cm(-1). Reactivity of the polysaccharide C-atoms was determined by 13C NMR spectroscopy: For dextran this was C-3 > C-2 > C-4, while for pullulan it was C-6 > C-3 > C-2 > C-4.
