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Marine macroalgae are efficient producers of sulfated polysaccharides. The algal sulfated polysaccharides possess diverse bioactivities and peculiar chemical structures, and represent a great potential source to be explored. In the present study, a heparinoid-active sulfated polysaccharide was isolated from the green alga Cladophora oligoclada. Results of chemical and spectroscopic analyses indicated that the sulfated polysaccharide was composed of →6)-ß-d-Galp-(1→, ß-d-Galp-(1→, →6)-α-d-Glcp-(1→ and →3)-ß-d-Galp-(1→ units with sulfate esters at C-2/C-4 of →6)-ß-d-Galp-(1→, C-6 of →3)-ß-d-Galp-(1→ and C-3 of →6)-α-d-Glcp-(1→ units. The branches consisting of ß-d-Galp-(1→ and →6)-ß-d-Galp-(1→ units were located in C-3 of →6)-ß-d-Galp-(1→ units. The sulfated polysaccharide exhibited potent anticoagulant activity in vitro and in vivo as evaluated by activated partial thromboplastin time (APTT), thrombin time, and the fibrinogen level. For the APTT, the signal for clotting time was more than 200 s at 100 µg/mL in vitro and at 15 mg/kg in vivo. The obvious thrombolytic activity of the sulfated polysaccharide in vitro was also found. The mechanism analysis of anticoagulant action demonstrated that the sulfated polysaccharide significantly inhibited the activities of all intrinsic coagulation factors, which were less than 1.0% at 50 µg/mL, but selectively inhibited common coagulation factors. Furthermore, the sulfated polysaccharide strongly stimulated the inhibition of thrombin by potentiating antithrombin-III (AT-III) or heparin cofactor-II, and it also largely promoted the inhibition of factor Xa mediated by AT-III. These results revealed that the sulfated polysaccharide from C. oligoclada had potential to become an anticoagulant agent for prevention and therapy of thrombotic diseases.

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Sulfated polysaccharides from marine algae have high potential as promising candidates for marine drug development. In this study, a homogeneous sulfated polysaccharide from the marine green alga Monostroma nitidum, designated MS-1, was isolated using water extraction and anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that MS-1 mainly consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ residues, with additional branches consisting of 4-linked ß-d-xylose, 4-/6-linked d-glucose, terminal ß-d-glucuronic acid, and 3-/2-linked α-l-rhamnose. Sulfate ester groups substituted mainly at C-2/C-4 of →3)-α-l-Rhap-(1→ and C-4 of →2)-α-l-Rhap-(1→ residues, slightly at C-2 of terminal ß-d-glucuronic residues. MS-1 exhibited strong anticoagulant activity in vitro and in vivo as evaluated by the activated partial thromboplastin time and thrombin time assays, and significantly decreased platelet aggregation. The anticoagulant activity mechanism of MS-1 was mainly attributed to strong potentiation thrombin by heparin cofactor-II, and it also hastened thrombin and coagulation factor Xa inhibitions by potentiating antithrombin-III. MS-1 possessed markedly thrombolytic activity evaluated by plasminogen activator inhibitior-1, fibrin degradation products, and D-dimer levels using rats plasma, and recanalization rate by FeCl3-induced carotid artery thrombosis in mice. MS-1 exhibited strong antithrombotic activity in vitro and in vivo evaluated by the wet weighs and lengths of thrombus, and thrombus occlusion time by electrically-induced carotid artery thrombosis in rats. These results suggested that MS-1 could be a promising marine drug for prevention and therapy of thromboembolic disease.

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Heparin has been used as first-line anticoagulant clinically for 80 years. Heparin mainly exerts its anticoagulant activity through interaction with ATIII. It has been found there are more than one hundred heparin-dependent functional proteins which demonstrates promising novel application beyond anticoagulant, such as anti-tumor, anti-malaria anti-inflammation, anti-viral, anti-malaria anti-anemia, etc. Heparin is also hopeful to be used as tool for drug delivery vehicle and functionalized implants material. In addition, heparin oligosaccharides are expected to be produced by chemical/enzymatic and bioengineering synthesis. Above mentioned new developments of heparin are covered in this review.

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Heparin-like membranes (CPBS) with nanofibers (approximate diameters of 100-500 nm) were prepared through electrospinning of a blended solution of carboxymethyl chitosan nanoparticle (CMCN, diameters 483 nm) and poly (vinyl alcohol) (CMCN/PVA) onto the surface of modified bacterial cellulose sulfate (BCS) membranes. SEM images confirmed that the CMCN were stretched to nanofibers during electrospinning. The presence of BCS on the collector of electrospinning machine increased the spinnability of CMCN/PVA solution. FTIR and XPS measurement revealed that there were SO3-, COO-, and OH groups on the surface of CPBS membrane, expressing structural similarity to heparin. CPBS membranes maintained hydrophilicity and the glutaraldehyde crosslinked CPBS membrane was stable in water. The clotting time and platelet adhesion experiments expressed the anticoagulant properties of CPBS. The APTT, TT and PT of CPBS increased up to 116.0%, 189.8%, and 50% than those of the plasma, (67.4 s, 16.2 s, and 48.4 s, respectively). No platelets adhered onto the surface of CPBS. An inflammatory response was determined according to activation of the macrophages seeded onto the membranes.

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Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, the polymeric repeat units and anticoagulant property in vitro and in vivo of SPm were investigated. SPm was a sulfated polysaccharide which was mainly constituted by 3-linked, 2-linked-α-l-rhamnose residues with partially sulfate groups at C-2 of 3-linked α-l-rhamnose residues and C-3 of 2-linked α-l-rhamnose residues. Small amounts of xylose and glucuronic acid exist in the forms of ß-d-Xylp(4SO4)-(1→ and ß-d-GlcA-(1→. SPm effectively prolonged clotting time as evaluated by the activated partial thromboplastin time and thrombin time assays, and exhibited strong anticoagulant activity in vitro and in vivo. The fibrin(ogen)olytic and thrombolytic properties of SPm were evaluated by plasminogen activator inhibitior-1, fibrin degradation products, D-dimer and clot lytic rate assays using rats plasma, and the results showed that SPm possessed high fibrin(ogen)olytic and thrombolytic properties. These results suggested that SPm has potential as a novel anticoagulant agent.

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Abstracts Here we report the anticoagulant property of Sulfonated Silk Fibroin (SSF) which was improved by sulfonation method. Chlorosulfonic acid was applied to modify the Silk Fibroin (SF) anticoagulant property by the preparation of the SSF. The SSF was prepared in the new technology that 50 °C, 0.2 g SF/ml chlorosulfonic acid and 15 h were optimized with the reaction temperature, special concentration ratio of the SF to the chlorosulfonic acid and the certain reaction time, respectively. Then the SF reaction solution was dialyzed, and freeze-dried to form the SSF. The different properties of the SF and the SSF have been revealed by Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Photoelectron Spectrometer (XPS), Gel Permeation Chromatography (GPC), X-ray Diffraction (XRD), Activated Partial Thromboplastin Time (APTT) etc. That the sulfonic acid groups were successfully induced into the SF molecular chains has also been verified. The SSF possessed the excellent performance on the APTT value, and it can be slowly released from the Poly(epsilon-caprolactone) (PCL) composite film. In conclusion, the SSF is the novel product modified by the chlorosulfonic acid directly, and it possesses the good anti-coagulation, resulting in that it can become one of candidates of anti-coagulation materials.

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A homogeneous polysaccharide was obtained from Monostroma angicava Kjellm by water extraction, preparative anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that the polysaccharide was a glucuronic acid-containing rhamnan-type sulfated polysaccharide. The backbone mainly consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ residues, partially sulfated at C-2 of →3)-α-l-Rhap-(1→ and C-3/C-4 of →2)-α-l-Rhap-(1→. The branching contained unsulfated or monosulfated 3-linked, 2-linked, 4-linked α-l-rhamnose and terminal ß-d-glucuronic acid residues. The polysaccharide had strong antidiabetic activity assessed by glucose consumption, total cholesterol and triglyceride levels using human hepatocellular carcinoma (HepG2) and insulin-resistant HepG2 cells. The polysaccharide exhibited high anticoagulant property by activated partial thromboplastin time and thrombin time assays, and possessed high fibrin(ogen)olytic activity evaluated by plasminogen activator inhibitior-1, fibrin(ogen) degradation products and D-dimer levels using rats plasma. The investigation demonstrated that the polysaccharide from Monostroma angicava Kjellm was a novel sulfated rhamnan and could be a potential antidiabetic and anticoagulant polysaccharide.

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