ABSTRACT
A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical "cage-like" ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/ß to prevent the activation of inflammasome NLRP3.
Subject(s)
Colitis , NF-kappa B , Humans , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Hydrogels , Galectin 3 , Colitis/metabolism , Inflammasomes/metabolism , Pectins/pharmacologyABSTRACT
Cardiovascular diseases are associated with platelet hyperactivity, and downregulating platelet activation is one of the promising antithrombotic strategies. This study newly extracted two polysaccharides (purified exopolysaccharides, EPSp and purified intercellular exopolysaccharides, IPSp) from Cordyceps sinensis Cs-4 mycelial fermentation powder, and investigated the effects of the two polysaccharides and their gut bacterial metabolites on platelet functions and thrombus formation. EPSp and IPSp are majorly composed of galactose, mannose, glucose, and arabinose. Both EPSp and IPSp mainly contain 4-Galp and 4-Glcp glycosidic linkages. EPSp and IPSp significantly inhibited human platelet activation and aggregation with a dose-dependent manner, and attenuated thrombus formation in mice without increasing bleeding risk. Furthermore, the EPSp and IPSp after fecal fermentation showed enhanced platelet inhibitory effects. The results have demonstrated the potential value of Cs-4 polysaccharides as novel protective ingredients for cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Cordyceps , Thrombosis , Mice , Humans , Animals , Galactose/metabolism , Fibrinolytic Agents/metabolism , Mannose/metabolism , Arabinose , Powders , Polysaccharides/pharmacology , Polysaccharides/metabolism , Cordyceps/metabolism , Thrombosis/drug therapy , Glucose/metabolismABSTRACT
This study assessed the protective effects of konjac glucomannan (KGM) on gut microbiome against the antibiotic perturbation in C57BL/6J mice. The native KGM (1.82 × 107) was partially hydrolyzed by endo-1,4-ß-mannanase, and two hydrolyzed fractions (KGM-eM with 3.82 × 105 Da and KGM-eL with 8.27 × 103 Da) were characterized and applied to mice with perturbation of antibiotics in comparison with the native KGM. The results showed that the native KGM better maintained the microbial diversity and composition in feces, and increased the production of the individual and total SCFAs in feces and serum with perturbation of antibiotics. In contrast, KGM with lower MW (KGM-eM and KGM-eL) increased the proportion of Lactobacillus and SCFA production with no antibiotics, however, the prebiotic effects were eliminated with perturbation of antibiotics. These results have demonstrated the protective effects of KGM with high MW on gut microbiome against the antibiotic perturbation in vivo.
Subject(s)
Gastrointestinal Microbiome , Animals , Anti-Bacterial Agents/pharmacology , Mannans/pharmacology , Mice , Mice, Inbred C57BLABSTRACT
This study investigated the effect of konjac glucomannan (KGM) of different molecular weight on fecal microflora against antibiotic disturbance. KGM (~1.8 × 107 Da) was partially hydrolysed with trifluoroacetic acid (TFA) for 10 and 60 min to KGM1 (~2.1 × 104 Da) and KGM2 (7413 Da), respectively. The acid treatment caused significant reduction of intrinsic viscosity, average molecular weight (MW) and particle size of KGM, but brought limited change to the molecular structure. Low-MW KGM2 showed the most significant effect on fecal microflora in the presence of two common antibiotics (ampicillin and clindamycin), by increasing the relative abundance of Bifidobacteriaceae while decreasing the proportion of Enterobacteriaceae. Additionally, both the native and acid-treated KGM counteracted the adverse influence of antibiotics on the production of short chain fatty acids. The results have demonstrated the effect of KGM on gut microbiota with antibiotic disturbance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Feces/microbiology , Gastrointestinal Microbiome/drug effects , Mannans/pharmacology , Amorphophallus/chemistry , Anti-Bacterial Agents/adverse effects , Bifidobacterium/drug effects , Enterobacteriaceae/drug effects , Fatty Acids, Volatile/metabolism , Fermentation , Humans , Hydrolysis , Mannans/chemistry , Molecular Structure , Molecular Weight , Particle Size , Trifluoroacetic Acid/chemistry , ViscosityABSTRACT
A pectin-rich dietary fiber from sisal waste (P-SF), containing 11.8% pectin, was produced by a sequential enzymatic-ultrasonic process. P-SF was effective in adsorbing Pb2+ from aqueous solution with a maximum adsorption amount of 184 mg g-1. Adsorption isotherms were fitted well by the Langmuir equation, and the adsorption kinetics could be described by a pseudo-second-order model. X-ray photoelectron spectroscopy and energy dispersive spectroscopy suggested that Pb2+ was adsorbed by P-SF via ion exchange, complexation and mineral precipitation. Dietary supplementation with 10% (w/w) P-SF in basal feed led to a significant decrease in Pb2+ in the brain, liver and kidney. P-SF has greater in vivo efficacy of Pb2+ removal as compared to commercial soybean dietary fiber. The reduction of brain Pb2+ level by P-SF was as effective as by a Pb2+ excretion drug. These findings suggested that P-SF has a great potential to be used as a dietary supplement to cope with Pb2+ poisoning.
Subject(s)
Agave/chemistry , Dietary Fiber/metabolism , Lead , Pectins , Adsorption , Animals , Brain/metabolism , Brain Chemistry , Disease Models, Animal , Environmental Pollutants/analysis , Environmental Pollutants/chemistry , Environmental Pollutants/isolation & purification , Environmental Pollutants/metabolism , Female , Lead/analysis , Lead/chemistry , Lead/isolation & purification , Lead/metabolism , Lead Poisoning , Mice , Mice, Inbred C57BL , Pectins/chemistry , Pectins/metabolism , SonicationABSTRACT
Two modified citrus pectins, MCP4 and MCP10, were prepared by UV/H2O2 treatment at pH 4 and pH 10, respectively, and their structures were characterized. MCP10 had a rhamnogalacturonan-I (RG-I) enriched backbone with a high degree of branching (DB â¼61 %) and a low methoxylation degree (24 %). MCP4 had a homogalacturonan enriched backbone with a high degree (46 %) of methoxylation and a low DB (â¼41 %) of RG-I branches. MCP10 exhibited a higher anti-inflammatory activity than MCP4 in suppressing the NF-κB expression and the production of pro-inflammatory factors TNF-α and IL-1ß of THP-1 cells stimulated by lipopolysaccharide. MCP10 also showed a stronger inhibitory effect on Caco-2 cell proliferation. The stronger bioactivities of MCP10 may be attributable to the abundant branches and the proper length of terminal galactan residues attached to the RG-I domain.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Colonic Neoplasms/drug therapy , Hydrogen Peroxide/chemistry , Inflammation/drug therapy , Pectins/pharmacology , Ultraviolet Rays , Acids/chemistry , Alkalies/chemistry , Anti-Inflammatory Agents/chemistry , Antineoplastic Agents/chemistry , Caco-2 Cells , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Humans , In Vitro Techniques , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Pectins/chemistryABSTRACT
Purpose: We hypothesized that increased level of serum ß2-microglobulin (ß2M) is an independent factor associated with higher mortality in hospitalized patients with exacerbated chronic obstructive pulmonary disease (COPD). Patients and Methods: We retrospectively analyzed 488 hospitalized patients with exacerbated COPD as the first diagnosis at Beijing Chao-Yang hospital, P. R. China between December 31st, 2012 and December 28th, 2017. Concentrations of serum ß2M and other clinical indexes were measured or collected on admission, and all patients were followed up to 90 days. The relationship between ß2M and 30- and 90-day all-cause mortality was explored by Cox regression analysis adjusted for age, C-reactive protein values, N-terminal pro-brain natriuretic peptide/100, respiratory failure [RF, defined as partial arterial oxygen pressure (PaO2) <60 mmHg on room air or PaO2 over the fraction of inspired oxygen (PaO2/FiO2) < 300], eosinopenia, consolidation, and acidaemia. Results: Median concentrations of ß2M were significantly higher in non-survivals compared to survivals within 30 days (4.11 mg/L (IQR 3.10-6.60) vs 2.79mg/L (IQR 2.13-3.76), P < 0.001) and 90 days (3.79 mg/L (IQR 2.61-6.69) vs 2.79 mg/L (IQR 2.13-3.73), P < 0.001). Serum levels of ß2M were correlated with 30-day and 90-day mortality in overall exacerbated COPD patients, with hazard ratios (HRs) of 1.09 (95% CI 1.04-1.14, P = 0.001) and 1.09 (95% CI 1.05-1.14, P < 0.001). In exacerbated COPD patients without RF and with RF, the HRs were 1.06 (95% CI 0.995-1.137, P = 0.069) and 1.14 (95% CI 1.02-1.27, P = 0.021) for 30-day mortality, 1.09 (95% CI 1.02-1.15, P = 0.010) and 1.14 (95% CI 1.03-1.26, P = 0.014) for 90-day mortality, respectively. Conclusion: Our data showed that concentrations of serum ß2M were associated with an increased risk of mortality, suggesting that ß2M might be a valuable predictor of poor prognosis for hospitalized patients with exacerbated COPD.
Subject(s)
Pulmonary Disease, Chronic Obstructive , beta 2-Microglobulin/blood , C-Reactive Protein/analysis , China/epidemiology , Humans , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/mortality , Retrospective StudiesABSTRACT
This study was to assess the protective effect of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1 on Bifidobacteria against antibiotic inhibition. The high-molecular weight EPS fractions showed significant protective effect on all five bifidobacterial strains against four common antibiotics, leading to a dramatic increase in the minimal inhibitory and minimal bactericidal concentrations. The protective effect of EPS on the bacteria was probably attributed to the formation of a viscous layer around the bacterial cell resisting the access by the antibiotics. The EPS layer surrounding the bacteria cell also promoted the aggregation of bacteria and formation of biofilm as observed by microscopy. EPS also enhanced the bifidobacterial adhesion to Caco-2 cell monolayer. In general, the protective effect as well as biofilm formation due to EPS was significantly correlated with the molecular weight of EPS fractions.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bifidobacterium/drug effects , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/pharmacology , Molecular Weight , Bacterial Adhesion , Bifidobacterium/ultrastructure , Biofilms/drug effects , Caco-2 Cells , Fermentation , Humans , Microscopy, Atomic ForceABSTRACT
This work studied a concurrent UV photocatalysis and alkaline H2O2 pretreatment (UHP) to enhance the subsequent enzymatic hydrolysis of sisal waste in comparison with alkaline H2O2 pretreatment (AHP). An optimal condition was identified for UHP at H2O2 charge 0.1â¯g/g dried sisal waste, pH 10.0, and UV radiation for 6â¯h. Under this condition, UHP led to a delignification rate of 76.6%, a conversion to reducing sugar at 71.2%, and a conversion to glucose at 91.6%, respectively. XRD, FT-IR and SEM analysis showed an increase in crystalline degree and significant changes in the structure of sisal during UHP. The current study implicates that UHP is more efficient than AHP in pretreating sisal waste, with reduced H2O2 charge, shortened pretreatment time, and enhanced enzymatic digestibility.
Subject(s)
Hydrogen Peroxide , Refuse Disposal , Ultraviolet Rays , Carbohydrates , Hydrolysis , Photochemical Processes , Spectroscopy, Fourier Transform InfraredABSTRACT
Fatigue is the symptom of tiredness caused by physical and/or psychological stresses. As fatigue is becoming a serious problem in the modern society affecting human health, work efficiency, and quality of life, effective antifatigue remedies other than pharmacological drugs or therapies are highly needed. Mushrooms have been widely used as health foods, because of their various bioactive constituents such as polysaccharides, proteins, vitamins, minerals, and dietary fiber. This paper reviews the major findings from previous studies on the antifatigue effects, the active components of mushrooms, and the possible mechanisms. Many studies have demonstrated the antifatigue effects of edible and medicinal mushrooms. These mushrooms probably mitigate human fatigue through effects on the functional systems, including the muscular, cardiovascular, hormone, and immune system. The bioactive constituents that contribute to the antifatigue effects of mushrooms may include polysaccharides, peptides, nucleosides, phenolic compounds, and triterpenoids. Further research is still needed to identify the active ingredients and to investigate their mechanism of action on the antifatigue effects. Since most previous studies have been carried out in animal models, more human trials should be performed to verify the antifatigue function of edible and medicinal mushrooms.
Subject(s)
Agaricales/chemistry , Fatigue/drug therapy , Plants, Medicinal/chemistry , Polysaccharides/therapeutic use , Dietary Fiber/therapeutic use , Fatigue/pathology , Humans , Minerals/chemistry , Minerals/therapeutic use , Polysaccharides/chemistry , Proteins/chemistry , Proteins/therapeutic use , Quality of Life , Vitamins/chemistry , Vitamins/therapeutic useABSTRACT
BACKGROUND: Anxiety and depression are two of the commonest and most modifiable comorbidities of chronic obstructive pulmonary disease (COPD) and have an independent effect on health and prognosis. FEV1% has been shown to be a poor predictor of anxiety and depression. The body mass index, degree of airflow obstruction, dyspnea, and exercise capacity (BODE) index is a multidimensional assessment system which may predict health outcome in COPD patients. The purpose of this study was to investigate the predictive validity of the BODE index for anxious and depressive symptoms in COPD patients. METHODS: This was a multicenter prospective cross-sectional study in 256 patients with stable COPD. Anxious and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). The relationships between anxiety, depression and potential predictors (including the BODE index) were analyzed by a binary Logistic regression model. RESULTS: Subjects who were anxious and depressive walked a shorter six-minute walking distance (6MWD), had more dyspnea, a higher BODE index, and lower health-related quality of life (P < 0.01). Anxiety and depression score was significantly correlated with BODE index, respectively (r = 0.335, P < 0.001; r = 0.306, P < 0.001). The prevalence of anxiety and depression increased with BODE stage increasing (P < 0.05). On the basis of binary Logistic regression, the BODE index was a good and independent predictor of anxiety and depression because it comprised dyspnea and 6MWD, which were shown to be the main determinants. CONCLUSIONS: The predictive validity of the BODE index for anxiety and depression was demonstrated. We propose that the BODE index should be included in assessment of COPD severity.
Subject(s)
Anxiety/diagnosis , Depression/diagnosis , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/psychology , Cross-Sectional Studies , Humans , Multivariate Analysis , Prospective StudiesABSTRACT
High-power ultrasound (20 kHz) was applied to modify the physicochemical properties of a high-molecular weight (MW) exopolysaccharide (EPS) from mycelial culture of a medicinal fungus. At 35 W/cm(2) or higher ultrasound power, the apparent and intrinsic viscosities of EPS solution dropped by nearly 85% within 10 min, and the water solubility was increased by more than fourfold. The ultrasonic treatment led to a notable reduction of the maximum MW and a more uniform MW distribution, but no significant change in the primary structure of the EPS molecules. In contrast, the intrinsic viscosity of EPS was reduced by only 20% in 1.0M sulfuric acid at 50 degrees C for 9h. Ultrasound was proven an effective and favorable means for improving the solution properties of high-MW bioactive polysaccharides in mild conditions.
Subject(s)
Fungi/metabolism , Polysaccharides/chemistry , Ultrasonics , Cell Line , Congo Red/pharmacology , Humans , Hydrolysis , Microscopy, Atomic Force/methods , Molecular Weight , Solubility , Sonication , Spectrophotometry, Infrared/methods , Temperature , Time Factors , ViscosityABSTRACT
Homogeneous sulfation of bagasse cellulose (BC) with chlorosulfonic acid-dimethylformamide was accomplished in an ionic liquid 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl). The BCS products from the sulfation had degrees of substitution (DS) in the range of 0.52-2.95 and a simultaneous substitution pattern at C-6, C-2 and C-3 positions. The sulfated BCS attained significant anticoagulation activity, causing a dose-dependent prolongation of coagulation time and inhibition of FIIa and FXa activities in human plasma. The anticoagulation activity of BCS showed a positive correlation with DS, and some of the activity indexes exceeded those of heparin.
Subject(s)
Anticoagulants/pharmacology , Cellulose/metabolism , Cellulose/pharmacology , Ionic Liquids/metabolism , Sulfates/metabolism , Blood Coagulation/drug effects , Factor XIIa/antagonists & inhibitors , Factor Xa Inhibitors , Heparin/metabolism , Humans , Magnetic Resonance Spectroscopy , Thrombin TimeABSTRACT
AIM: To investigate the anticoagulant efficacy and mechanism of a semi-synthesized sodium beta-1,4-glucan sulfate (Na-MCS). METHODS: Anticoagulant activity was evaluated by means of coagulation assays in comparison with heparin. The anticoagulant mechanism of Na-MCS was disclosed by inhibitory analysis of the activities of coagulation factors using chromogenic substrates. RESULTS: 0.6 microg x mL(-1) Na-MCS could significantly prolong APTT and TT, but has less effect on PT at an even higher concentration. The dosage of Na-MCS required to double APTT of normal human plasma was 0.7 microg x mL(-1), lower than that of heparin with the activity of 150 u x mg(-1). CONCLUSION: Na-MCS represented a potent anticoagulation activity in vitro, which matched the efficacy of heparin in a certain range of concentrations. Na-MCS exhibited anticoagulant activity due to inhibition of the coagulation factors IIa and Xa by the mediation of anti-thrombin AT-III.
Subject(s)
Anticoagulants/pharmacology , Blood Coagulation/drug effects , Glucans/pharmacology , Anticoagulants/administration & dosage , Antithrombin III/pharmacology , Dose-Response Relationship, Drug , Factor Xa/metabolism , Glucans/administration & dosage , Heparin/pharmacology , Humans , Partial Thromboplastin Time , Prothrombin/metabolism , Prothrombin Time , Thrombin TimeABSTRACT
OBJECTIVE: To observe the effects of Dexamethasone (Dex), a synthetic glucocorticoid, on glucocorticoid receptor expression in the human ovarian carcinoma cell line 3AO. The molecular mechanism of glucocorticoid (GC) on 3AO cells was also studied. METHODS: The expression and regulation of the glucocorticoid receptor in 3AO cells was studied by utilizing radioligand binding assay and quantitative RT-PCR. RESULTS: High affinity and low capacity GR existed in 3AO cells, in addition, GR binding activity was down-regulated by Dex in a time-dependent manner, to a level about 28.34% of control following 24 hours treatment, with a concomitant decrease in GR mRNA. The induction of alkaline phosphatase (AKP) activity by Dex was reversed by RU486, a potent glucocorticoid antagonist. CONCLUSION: In 3AO cells, functional GR which can be down-regulated by Dex at the protein and mRNA level, exists suggesting that the regulating effects of Dex on GR occur at least partially at the GR mRNA level, and that the cellular effects of Dex on 3AO cells might be mediated by GR.