Search Results (7)

Fucoidan, a sulphated polysaccharide from brown seaweed composed of several monosaccharides, has been stated to have several bioactive properties such as antioxidant, antiviral, anticancer, antithrombic, anti-inflammatory, and immunomodulatory effects. This paper provides research findings on green extraction methods, structural analysis of fucoidan, and its associated bioactivities. Fucoidans from brown seaweeds, Fucus vesiculosus and Ascophyllum nodosum, were extracted using green solvents such as citric acid (CA) followed by MWCO (molecular weight cut-off) filtration to obtain high-purity polysaccharides. The presence of functional groups typical to fucoidans, namely, fucose, sulfate, and glycosidic bonds, in the extracts were confirmed through the data obtained from FTIR (Fourier-transform infrared spectroscopy), TGA (thermogravimetric analysis), DSC (differential scanning calorimetry), and solid-state CP–MAS (cross-polarization magic angle spinning) analysis. The MWCO analysis identified that the >300 kDa fraction can have better content of fucoidan (FV-CA 79.16%, FV-HCl 63.59%, AN-CA 79.21%, AN-HCl 80.70%) than the conventional extraction process. Furthermore, the >300 kDa fraction showed significantly higher antioxidant activities compared to crude fucoidan extracts. Crude fucoidan extracts showed significant inhibition of cell viability in human lung (A459 lung carcinoma cells) and colorectal adenocarcinoma (Caco-2) cells at higher concentrations. The fucoidan extracted with green solvents and avoiding alcohol-based precipitation has substantial antioxidant/antitumor action, so, due to this activity, it can be employed as functional foods in food applications. Full article

The development of novel anticoagulants requires a comprehensive investigational approach that is capable of characterizing different aspects of antithrombotic activity. The necessary experiments include both in vitro assays and studies on animal models. The required in vivo approaches include the assessment of pharmacokinetic and pharmacodynamic profiles and studies of hemorrhagic and antithrombotic effects. Comparison of anticoagulants with different mechanisms of action and administration types requires unification of the experiment scheme and its adaptation to existing laboratory conditions. The rodent thrombosis models in combination with the assessment of hemostasis parameters and hematological analysis are the classic methods for conducting preclinical studies. We report an approach for the comparative study of the activity of different anticoagulants in vivo, including the investigation of pharmacodynamics and the assessment of hemorrhagic effects (tail-cut bleeding model) and pathological thrombus formation (inferior vena cava stenosis model of venous thrombosis). The reproducibility and uniformity of our set of experiments were illustrated on unfractionated heparin and dabigatran etexilate (the most common pharmaceuticals in antithrombic therapy) as comparator drugs and an experimental drug variegin from the tick Amblyomma variegatum. Variegin is notorious since it is a potential analogue of bivalirudin (Angiomax, Novartis AG, Basel, Switzerland), which is now being actively introduced into antithrombotic therapy. Full article

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent. Full article

From a structural point of view, hydrocolloids are characterized as hydrophilic biopolymers with high molecular weight. Hydrocolloids are widely used in the food industry, mainly as thickeners, gelling agents, stabilizers of foams and emulsions, and inhibitors of ice and sugar crystals. Additionally, hydrocolloids are being increasingly used as fat replacers, aiming to produce low-calorie foods. Besides these important functional properties in different food products, hydrocolloids are being progressively recognized for their diverse biological properties, including anticoagulant, antithrombic, hypocholesterolemic, antioxidant, antiviral, antitumor, and immunomodulatory effects. Additionally, some studies have reported that these biopolymers have beneficial effects against a significant number of dermatological problems. Regarding antiviral properties, some hydrocolloids, such as sulfated polysaccharides, exhibit unique structures that exert these effects. This study aims to describe the corresponding underlying mechanisms of this bioactivity. Special attention will be given to the way hydrocolloids may obstruct different phases of the viral life cycle (attachment, penetration, uncoating, biosynthesis, viral assembly, and release) by directly inactivating virions before infection or by inhibiting its replication inside the host cell. The presented information might represent a potential contribution to the discovery and development of new antiviral drugs. Full article

Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H₂O₂ production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection. Full article

Objectives: Patients with peripheral arterial occlusive disease (PAOD) are at risk of worsening limb symptoms, major adverse cardiovascular events and exhibit an impaired life expectancy. There is a lack of evidence on the extent of pharmacological secondary prevention in PAOD patients. This study assesses treatment patterns of antithrombotic agents in symptomatic PAOD patients. Methods: This is a retrospective cohort study using data from the second largest insurance fund in Germany, BARMER. We included symptomatic PAOD patients undergoing in-hospital treatment with an index admission between 1 January 2010 and 31 December 2017. Outcomes were proportions of single antiplatelets (SAPT), dual antiplatelets (DAPT), vitamin-K antagonists (VKA), or direct oral anticoagulants (DOAC) in the 12 months prior and 6 months after the index hospitalization. Non-parametric cumulative incidence for competing risks was estimated to account for censoring and death after discharge from hospital stay. Patient flows were visualised by alluvial diagrams. All analyses were stratified by intermittent claudication (IC) and chronic limb-threatening ischaemia (CLTI). The protocol was registered to ClinicalTrials.gov (NCT03909022). Results: A total of 80,426 unique patient encounters were identified. Mean age was 72.7 (46.3% female). Amongst all patients, 25.6% were on SAPT, 4.1% on DAPT, 9.1% on VKA, 3.9% on DOAC, 3.9% on both antiplatelets and oral anticoagulation, and 53.3% without any antithrombotic therapy during the 12 months before index stay. The estimated cumulative incidence was 37.9% SAPT, 14.8% DAPT, 7.5% VKA, 4.3% DOAC, 7.4% both, and 28.1% without any antithrombotic therapy during the 6 months after index stay. The considerable increases in antiplatelet therapy were mainly driven by the group of patients without antithrombotics before index stay. As compared with IC, patients who suffered from CLTI received less often antiplatelets but more often anticoagulants both before and after index stay. Conclusions: Utilisation rates of antithrombotic therapy increased considerably after in-hospital treatment for PAOD. Yet, remarkably high rates of symptomatic patients without any blood-thinning therapy constitute a major concern with respect to adequate secondary prevention of PAOD patients. Full article

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment. Full article