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Excessive secretion of human islet amyloid polypeptide (hIAPP) is an important pathological basis of diabetic encephalopathy (DE). In this study, we aimed to investigate the potential implications of hIAPP in DE pathogenesis. Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function. We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus. In vitro assays revealed that oligodendrocytes, compared with neurons, were more prone to acidosis under exogenous hIAPP stimulation. Moreover, western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter (MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70. Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2 (YIPF2, which modulates the transfer of CD147 to the cell membrane) as a significant target. Furthermore, YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice. These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding, potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.
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The aim of this study was to prepare a drug carrier that could deliver oral insulin to the intestine. A hydrogel beads composed of sodium carboxymethyl cellulose (CMC), Zingiber offtcinale polysaccharide (ZOP) and chitosan (CS) were prepared by ionic gel method as insulin carrier. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and thermogravimetric (TGA) showed that the hydrogel was formed by metal ion coordination between ZOP and CMC and Fe3+, and CS was coated on the surface of the hydrogel ball in the form of non covalent bond. The results showed that the swelling process of hydrogel spheres has significant pH sensitivity. In addition, the hydrogel beads successfully coated insulin, and the drug loading rate (DL) of (ZOP/CMC-Fe3+)@CS could reach 69.43 ± 7.32 mg/g, and the entrapment efficiency (EE) could reach 66.94 ± 7.43 %. In vitro release experiments, the release rate of (CMC/ZOP-Fe3+)@CS in simulated gastric fluid (SGF) for 2 h was <20 %, and the cumulative release rate of insulin after 9 h in simulated intestinal fluid (SIF) reached over 90 %. The results showed that the hydrogel beads prepared in this work could be used as a potential carrier for delivering oral insulin.
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Compuestos de Azabiciclo , Quitosano , Piperazinas , Zingiber officinale , Hidrogeles/química , Liberación de Fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Portadores de Fármacos/química , Polisacáridos , Insulina , Concentración de Iones de Hidrógeno , Quitosano/químicaRESUMEN
Astrocytes transfer extracellular functional mitochondria into neurons to rescue injured neurons after a stroke. However, there are no reports on drugs that interfere with intercellular mitochondrial transfer. Chrysophanol (CHR) was an effective drug for the treatment of cerebral ischemia-reperfusion injury (CIRI) and was selected as the test drug. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model and the middle cerebral artery occlusion animal model were established to investigate the effect of CHR on CIRI. The result showed that astrocytes could act as mitochondrial donors to ameliorate neuronal injury. Additionally, the neuroprotective effect of astrocytes was enhanced by CHR, the CHR improved the neuronal mitochondrial function, decreased the neurological deficit score and infarction volume, recovered cell morphology in ischemic penumbra. The mitochondrial fluorescence probe labeling technique has shown that the protective effect of CHR is associated with accelerated astrocytic mitochondrial transfer to neurons. The intercellular mitochondrial transfer may be an important way to ameliorate ischemic brain injury and be used as a key target for drug treatment.
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Antraquinonas , Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Isquemia Encefálica/metabolismo , Astrocitos/metabolismo , Daño por Reperfusión/metabolismo , Neuronas/metabolismo , MitocondriasRESUMEN
An acidic polysaccharide (SMP) with a molecular weight (Mw) of 1.28 × 106 Da was isolated from Salvia miltiorrhiza. The monosaccharide composition in molar percentages was rhamnose (Rha): galacturonic acid (GalA): galactose (Gal): arabinose (Ara) = 6.15: 55.98: 21.27: 16.69. The results of simulated digestion in vitro showed that SMP was not degraded in saliva, gastric juice or intestinal juice. The Y maze test and new object recognition test showed that SMP could improve the working memory impairment of aging mice. SMP could also increase the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and brain tissue, decrease the content of malondialdehyde (MDA), decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue, and increase the content of short-chain fatty acids (SCFA) in the intestine. In addition, SMP could also regulate the intestinal flora structure, including increasing the relative abundance of Firmicutes and Bacteroidetes and decreasing the relative abundance of Proteobacteria. This work lays a foundation for the development of functional foods related to Salvia miltiorrhiza.
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Salvia miltiorrhiza , Ratones , Animales , Salvia miltiorrhiza/química , Polisacáridos/farmacología , Polisacáridos/química , Monosacáridos/química , Superóxido Dismutasa , DigestiónRESUMEN
Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze-thaw-assisted extraction (FAE) were used to extract PSPs, and their structure-activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure-activity relationship of PSPs.
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Crataegus pinnatifida is a common food in China, Europe and North America. In order to confirm polysaccharide was the material basis for C. pinnatifida to exert immune regulation. A polysaccharide (CPP) with a molecular weight of 13.58 kDa was isolated from C. pinnatifida. The structure of CPP was determined to be a backbone composed of â 3,5)-α-l-Araf-(1â, with two branches consisting of â 4)-α-d-Galp-(1 â and â 5)-α-l-Araf-(1â, with α-l-Araf and α-d-Manp as the terminal unit. CPP (10 â¼ 500 µg/mL) could promote the secretion of nitric oxide, interleukin-2, interleukin-6 and tumor necrosis factor-α in vitro. CPP could significantly restore the body weight of immunosuppressive mice and improve the immune organ index and interleukin-2, interleukin-6, and tumor necrosis factor-α secretion. In addition, CPP increased the abundance of Bacteroidetes and Verrucomicrobia and decreased the abundance of Proteobacteria at the phylum level. So CPP can regulate the gut microbiota and play an important role in immune regulation.
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Crataegus , Microbioma Gastrointestinal , Ratones , Animales , Interleucina-6/análisis , Interleucina-2/análisis , Crataegus/química , Factor de Necrosis Tumoral alfa/análisis , Frutas/química , Polisacáridos/químicaRESUMEN
Polysaccharide was one of the considered major active ingredient in Polygonatum odoratum which was crucial for its quality evaluation. In this study, High performance liquid chromatography (HPLC) combined with chemometrics methods were performed to assess the quality of P. odoratum polysaccharide (POP) harvested from different locations. The methodology validation and similarity evaluation results showed that the analysis method was able to meet the requirement of fingerprint analysis, and 10 batches of POPs had a high degree of similarity based on the similarity values were greater than 0.960. The results of hierarchical cluster analysis (HCA) showed that different regions POPs could be classified by clustering analysis based on their nuances. The results of principal component analysis (PCA) showed that the mannose (58.13%â¼78.18%) and glucuronic acid (2.36%â¼11.72%) could be selected as herb markers for the quality control of P. odoratum. In conclusion, a more quantitative quality control method was established, and could be applied to the identification and quality control of different P. odoratum and their products.
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Polysaccharides have received extensive attention due to their multiple physiological functions, especially their remarkable antioxidant capacity. In this study, a novel acidic polysaccharide (PSMP-2) with a molecular weight (Mw) of 1.28 × 106 Da from Salvia miltiorrhiza Bunge was extracted and purified via DEAE-52 cellulose column and Sephadex G-100 column chromatography. The structure of PSMP-2 was characterised by high-performance gel permeation chromatography (HPGPC), high-performance liquid chromatography (HPLC), Fourier transforms infrared spectroscopy (FT-IR) and methylation analysis. The results showed that PSMP-2 was an acidic heteropolysaccharide composed of rhamnose (Rha) (6.15%), galacturonic acid (GalA) (55.98%), and galactose (Gal) (21.27%) and arabinose (Ara) (16.69%). PSMP-2 contained five major glycosidic linkages, (1â)-linked-Ara, (1â2, 4)-linked-Rha, (1â4)-linked-Gal, (1â6)-linked-Gal, (1â3, 6)-linked-Gal, in a molar ratio of 5.98: 1.45: 72.23: 16.40: 3.94. The IC50 of PSMP-2 on 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl free radical scavenging ability were 0.991 mg/mL and 4.007 mg/mL, respectively. It could regulate the activity of antioxidant enzymes in vivo and had good antioxidant activity. To sum up, a novel acidic polysaccharide (Mw of 1.28 × 106 Da) with antioxidant activity was isolated from S. miltiorrhiza, and its application prospect in the field of medicine and food was preliminarily revealed.
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Antioxidantes , Salvia miltiorrhiza , Antioxidantes/química , Salvia miltiorrhiza/química , Espectroscopía Infrarroja por Transformada de Fourier , Polisacáridos/química , Galactosa/químicaRESUMEN
The structural characteristics, rheological properties, antioxidant and anti-inflammatory activities of Zingiber officinale polysaccharides (ZOP) and ZOP-1 were studied. The total soluble sugar contents of ZOP and ZOP-1 were 78.6 ± 0.6 and 79.4 ± 0.4%, respectively. Compared with ZOP, ZOP-1 had a larger molecular weight and a more uniform distribution. There were also some differences in the monosaccharide composition between ZOP and ZOP-1. The main monosaccharide of ZOP and ZOP-1 was glucose (Glc) and galactose (Gal), respectively. Ultraviolet visible spectroscopy (UV-Vis) and fourier transform infrared spectra (FT-IR) results showed that the two polysaccharides had the characteristic absorption peaks of polysaccharides and did not contain nucleic acid and protein. They had good thermal stability, trihelix structure and amorphous sheet structure. ZOP and ZOP-1 had obvious differences in microstructure. The surface of ZOP was smooth and the broken structure was compact and stable with angular shape, while the surface of ZOP-1 was uneven with spiral accumulation and not closely arranged. Moreover, ZOP and ZOP-1 were polysaccharides molecular polymers which were entangled by van der waals' force (VDW) between polysaccharides molecules and hydrogen bond association between sugar chains, and both contain α pyranose. At different concentrations, temperature, pH and salt ion concentrations, both ZOP and ZOP-1 had the properties of non-Newtonian fluids, showed shear dilution phenomenon, which had the potential as a texture modifier or thickener in food or biomedicine. Compared with ZOP, ZOP-1 showed superior antioxidant and anti-inflammatory activities in vitro.
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Antioxidantes , Zingiber officinale , Antioxidantes/química , Espectroscopía Infrarroja por Transformada de Fourier , Polisacáridos/química , MonosacáridosRESUMEN
Iron deficiency anemia can lead to a variety of functional disorders, which is one of the highest incidence of nutrient deficiency diseases. The direct addition of iron to food will not only brings difficulties to the production of products, but also brings damages to human body. In recent years, international studies have shown that polysaccharide iron complex (PIC) not only has a variety of pharmacological activities of polysaccharide itself, but also has the function of supplementing iron, so it is a good iron supplement. With the advantages of good solubility, high iron content, low gastrointestinal irritation and high bioavailability, PIC is an effective iron supplement for iron deficiency anemia and has attracted more and more attention. In this paper, the different preparation methods, structural characterization, biological activities and clinical applications of PIC synthesized by natural polysaccharides from plant were reviewed, in order to provide theoretical basis for the development and application of PIC.
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As a mental disease in modern society, depression shows an increasing occurrence, with low cure rate and high recurrence rate. It has become the most disabling disease in the world. At present, the treatment of depression is mainly based on drug therapy combined with psychological therapy, physical therapy, and other adjuvant therapy methods. Antidepressants are primarily administered peripherally (oral and intravenous) and have a slow onset of action. Antidepressant active ingredients, such as neuropeptides, natural active ingredients, and some chemical agents, are limited by factors such as the blood-brain barrier (BBB), first-pass metabolism, and extensive adverse effects caused by systemic administration. The potential anatomical link between the non-invasive nose-brain pathway and the lesion site of depression may provide a more attractive option for the delivery of antidepressant active ingredients. The purpose of this article is to describe the specific link between intranasal administration and depression, the challenges of intranasal administration, as well as studies of intranasal administration of antidepressant active ingredients.
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In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. These results manifested that DOP may be a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury.
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Most proteins given orally have low bioavailability and are easily eliminated by rapid metabolism in vivo. In order to immobilize the drug at the site of administration and delay its release, a natural, gentle release system was designed. In this study, a heteropolysaccharide (ZOP) was isolated from Zingiber officinale using an ultrasonic assisted extraction method. ZOP Ara = 1.97: 1.15: 94.33: 1.48: 1.07. The ZOP/Chitosan (CS) composite hydrogel was synthesized using epichlorohydrin (ECH) as a cross-linking agent. The structure, morphology, and water-holding capacity of the composite hydrogel were characterized. The data showed that the addition of ZOP improved the hardness and water-holding capacity of the material. A swelling ratio test showed that the prepared hydrogel was sensitive to pH and ionic strength. In addition, the degradation rate of the hydrogel in a phosphate-buffered saline (PBS) solution with a pH value of 1.2 was higher than that in PBS with pH value of 7.4. Similarly, the release kinetics of Bovine serum albumin (BSA) showed higher release in an acidic system by the hydrogel composed of ZOP/CS. The hydrogel prepared by this study provided a good microenvironment for protein delivery. In summary, this composite polysaccharide hydrogel is a promising protein-drug-delivery material.
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Coriolus is the dried fruiting body of Coriolus versicolor (L. ex Fr.) Quel. C. versicolor (CV) is a worldwide-distributed fungus, which is common and widely used in primitive forests in the northern hemisphere. Polysaccharide, as the main active ingredient in CV, has a variety of biological activities, such as promoting immune function, antivirus, antitumor, anti-diabetes, and so on. However, Coriolus versicolor polysaccharide (CVP) faces the problems of a single extraction method, lack of research on separation and purification, and the research on structural characterization is limited to the primary structure. Furthermore, the existing research results have not been systematically reviewed. Therefore, this paper summarizes the research status of CVP in terms of extraction technology, separation and purification, structural characterization, and pharmacological activity in recent years, in order to provide a theoretical basis for in-depth research, development, and utilization of CVP.
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A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. Using ZOP and ZOP-NPs as reductants and stabilizers, ZOP-AgNPs and ZOP-NPs-AgNPs were prepared. They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. And the zeta potential values of them were-19.4,-21.6,-19.7,-23.8mV, respectively. The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs.
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Hyperlipidemia is a chronic metabolic disease caused by the abnormal metabolism of lipoproteins in the human body. Its main hazard is to accelerate systemic atherosclerosis, which causes cerebrovascular diseases such as coronary heart disease and thrombosis. At the same time, although the current hypolipidemic drugs have a certain therapeutic effect, they have side effects such as liver damage and digestive tract discomfort. Many kinds of polysaccharides from natural resources possess therapeutic effects on hyperlipidemia but still lack a comprehensive understanding. In this paper, the research progress of natural polysaccharides on reducing blood lipids in recent years is reviewed. The pharmacological mechanisms and targets of natural polysaccharides are mainly introduced. The relationship between structure and hypolipidemic activity is also discussed in detail. This review will help to understand the value of polysaccharides in lowering blood lipids and provide guidance for the development and clinical application of new hypolipidemic drugs.
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Hiperlipidemias , Hipolipemiantes , Humanos , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/química , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Recursos Naturales , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/uso terapéuticoRESUMEN
This study investigated the structural elucidation, anti-radical and immunomodulatory activities of polysaccharides from the roots of Glehnia littoralis. A crude polysaccharide was extracted from the roots of G. littoralis through the ultrasonic-assisted extraction and further purified by DEAE-52 cellulose and Sephadex G-100 gel column, a major polysaccharide fraction named GLP80-1 was obtained. The chemical properties and structure of GLP and GLP80-1 were characterized by acid hydrolysis, methylation analysis, along with high performance gel permeation chromatography, Fourier transform infrared, nuclear magnetic resonance, scanning electron microscope, thermogravimetric analysis and X-ray diffraction. The molecular weight distributions of GLP were determined as 1.89 × 106 and 1.26 × 104 Da. The monosaccharide composition of GLP was glucose, glucuronic acid, galactose and arabinose with molar ratios of 0.91:0.04:0.03:0.02, respectively. The average molecular weight of GLP80-1 was determined as 1.63 × 104 Da. The structure of GLP80-1 was deduced to be a homogenous glucan, comprised a main chain of (1â4)-linked-α-D-Glcp with a single α-D-Glcp branch substituted at C-6. The results of biological activities in vitro showed that GLP and GLP80-1 exhibited free radical scavenging effects, and displayed promotion for the proliferation of mouse spleen lymphocytes and RAW264.7 cells. The data indicated that GLP and GLP80-1 had the potential to be explored as novel natural antioxidant and immunomodulator for application in functional food.
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Apiaceae , Polisacáridos , Animales , Antioxidantes/química , Ratones , Peso Molecular , Monosacáridos/química , Raíces de Plantas/química , Polisacáridos/químicaRESUMEN
A novel polysaccharide (GLP) with a molecular weight of 1.37 × 105 Da was purified from the roots of G. littoralis. Using monosaccharide composition, methylation analysis, GC-MS, 1D and 2D NMR, the structure of GLP was determined to be a 1 â 4)-α-D-Glcp glycoside linkage, while the terminal group of 1â)-α-D-Glcp was bonded to the main chain via O-6. Then, GLP-NPs were prepared by nano-precipitation method, the particle size of GLP-NPs was 288.4 nm and PDI was 0.340. GLP-NPs-AgNPs were prepared using GLP-NPs as reducing agent. GLP-NPs-AgNPs were characterized by ultraviolet-visible spectrophotometer (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM) and X-ray diffraction (XRD). The yield of GLP-NPs-AgNPs was 38.77%, the particle size was 12.5 nm and the chelation rate of silver nanoparticles with polysaccharides was 67.5%. GLP-NPs-AgNPs had better antioxidant and antibacterial activities than GLP and GLP-NPs. In the present work, a simple and eco-friendly approach for the synthesis of silver nanoparticles (AgNPs) using G. littoralis polysaccharides nanoparticles (GLP-NPs) as reducing agent.
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Antibacterianos/farmacología , Antioxidantes/farmacología , Apiaceae/química , Polisacáridos/farmacología , Plata/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Secuencia de Carbohidratos , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , Peso Molecular , Tamaño de la Partícula , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
The purpose of this work was to prepare and characterize Angiopep-2 functionalized ginsenoside-Rg3 loaded nanoparticles (ANG-Rg3-NP) and evaluate the therapeutic effect on C6 glioma cells. Nanoparticles were prepared by the emulsion solvent evaporation method. Angiopep-2 was functionalized to nanoparticles via a maleimide-thiol covalent binding reaction to obtain ANG-Rg3-NP. The prepared nanoparticles were evaluated for size, zeta potential, morphology, stability, encapsulation efficiency, loading capacity, and release properties. The cytotoxicity study and targeting effect of ANG-Rg3-NP were evaluated by MTT assay. The study of cellular uptake in C6 glioma cells was performed by fluorescence microscopy and by using a microplate reader. The prepared ANG-Rg3-NP was observed to be uniformly spherical in shape with a particle size at 147.1 ± 2.7 nm. The encapsulation efficiency and loading capacity reached 80.6 ± 3.0% and 27.2 ± 1.4%, respectively. Additionally, ANG-Rg3-NP exhibited a desirable sustained release behavior. In vitro cytotoxicity study indicated that ANG-Rg3-NP could inhibit the proliferation of C6 glioma cells in a concentration-dependent manner. Also, the functionalization of Angiopep-2 made nanoparticles cross the blood-brain barrier more easily and accelerated the cellular uptake of nanoparticles. The ANG-Rg3-NP was a promising brain drug delivery carrier for the treatment of glioma.
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Neoplasias Encefálicas/tratamiento farmacológico , Ginsenósidos/administración & dosificación , Glioma/tratamiento farmacológico , Péptidos/química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Ginsenósidos/química , Ginsenósidos/farmacología , Glioma/patología , Nanopartículas , Tamaño de la Partícula , Ratas , Ratas Sprague-DawleyRESUMEN
5-Fluorouracil (5-FU) is one of the most important agents used to treat colorectal cancer. However, the therapeutic effect of 5-FU on colon cancer is limited. SM-1 is a novel type of proapoptotic agent that directly activates procaspase-3 to caspase-3, leading to apoptosis in human cancer cells. The aim of the present study was to evaluate the antitumor effects of 5-FU in combination with SM-1. The human colorectal cancer cell lines HCT116 and LoVo were cultured in the presence of SM-1 and 5-FU. The combination of SM-1 and 5-FU treatment exhibited increased proliferation inhibitory effects compared with 5-FU treatment alone in HCT116 and LoVo cells, as determined using an MTT assay. SM-1 significantly decreased the half-maximal inhibitory concentration of 5-FU from 8.07±0.49 to 2.55±0.41 µmol/l in HCT116 cells, and from 7.90±0.98 to 3.14±0.81 µmol/l in LoVo cells. Similarly, the apoptotic activity was increased to 47.95 and 35.19% in HCT116 and LoVo cells, respectively, as determined using Annexin V/propidium iodide staining and flow cytometry. The combination of SM-1 and 5-FU treatment led to significantly increased caspase-3 activity compared with either compound alone. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis revealed the downregulation of B-cell lymphoma 2 and Survivin, and the upregulation of apoptosis regulator Bcl-2-associated X protein and cleaved poly (ADP-ribose) polymerase in HCT116 and LoVo cells. In addition, RT-qPCR identified downregulation of X-linked inhibitor of apoptosis protein mRNA. 5-FU and SM-1 treatment in combination increased tumor proliferation inhibition in HCT116 and LoVo xenograft mouse models of colorectal cancer, compared with SM-1 or 5-FU treatment alone. SM-1 significantly enhanced the antitumor activity of 5-FU in colorectal cancer. These improved effects were due to increased activity of the apoptotic signaling pathway.