scholarly journals An antithrombin-dependent sulfated polysaccharide isolated from the green alga Caulerpa cupressoides has in vivo anti- and prothrombotic effects

2011 ◽  
Vol 41 (4) ◽  
pp. 634-639 ◽  
Author(s):  
José Ariévilo Gurgel Rodrigues ◽  
Ismael Nilo Lino de Queiroz ◽  
Ana Luíza Gomes Quinderé ◽  
Bruno Cunha Vairo ◽  
Paulo Antônio de Souza Mourão ◽  
...  
Keyword(s):  
Body Weight ◽  
Green Algae ◽  
Red Algae ◽  
Sulfated Polysaccharide ◽  
Sulfated Polysaccharides ◽  
Antithrombotic Activity ◽  
Thrombin Inhibition ◽  
Antithrombotic Effects ◽  
Mechanism Of Interaction

Red algae sulfated polysaccharides (SPs) have been widely described as anticoagulant and antithrombotic agents; however no description of antithrombotic activity regarding green algae SPs has been reported. Caulerpa cupressoides (Chlorophyta) has three different SPs fractions (SP1, SP2 and SP3). We investigated the effects of SP2 on thrombin activity by antithrombin and in an experimental model of venous thrombosis in rats. The inhibition of thrombin assay was evaluated using antithrombin (AT) in the presence of SP2 and the antithrombotic activity was investigated in rats with thromboplastin as the thrombogenic stimulus. The anticoagulant effects of SP2 are suggested be due to the potentiation of thrombin inhibition by antithrombin (IC50 ~ 10.0µg mL-1) and this mechanism of interaction is different when compared to other studied Caulerpa polysaccharides. SP2 exhibited antithrombotic effects at doses of 1.0 and 2.0mg kg-1 body weight, but at higher doses (>2.0mg kg-1 body weight) this polysaccharide revert the antithrombotic property. No hemorrhagic effect (2.0mg kg-1) was observed. As occurs with red algae SPs, these results indicate that green algae SPs are also capable of exhibiting different in vivo properties.

INFLUENCE OF THE SULFATION PATTERN ON CERTAIN BIOLOGICAL PROPERTIES OF GALACTOSAMINOGLYCANS

1987 ◽  
Author(s):  
B Casu ◽  
L Marchese ◽  
A Naggi ◽  
G Torri ◽  
J Fareed ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Chlorosulfonic Acid ◽  
Biological Properties ◽  
Sulfated Polysaccharides ◽  
Low Molecular Weight ◽  
Antithrombotic Activity

In order to investigate the influence of charge distribution and chain length on the biological properties of sulfated polysaccharides, additional sulfate groups were introduced into the galactosaminoglycans, chondriotin sulfate and dermatan sulfate. Using a flexible method (with sulfuric acid and chlorosulfonic acid) for concurrent sulfation and controlled depolymerization, numerous products were obtained and characterized by chemical, enzymatic and nuclear magnetic resonance spectroscopic methods. The biologic actions of these products were profiled in both in vitro and in vivo assays for antithrombotic activity. Despite a weaker in vitro anticoagulant activity, low molecular weight over sulfated galactosaminoglycans produced significant dose-dependent antithrombotic actions in animal models which were similar to the actions observed with oversulfated low molecular weight heparins. These results suggest that a significant antithrombotic activity can be elicited through non-specific interactions of polysulfates with cellular and plasma components, and that clusters of sulfate groups such as the 4-6 disulfate group on D-galactosaminoglycan residues may be important for these interactions. Furthermore, these results, also suggest that supersulfation of glycosaminogly-cans results in products with biologic activity distinct from the native material.

INCREASED SULFATION IMPROVES THE ABILITY OF VESSEL WALL GLYCOSA-MINOGLYCANS TO REGULATE THROMBIN ACTIVITY AND PROTHROMBIN ACTIVATION IN PLASMA

1987 ◽  
Author(s):  
F A Ofosu ◽  
G J Modi ◽  
M A Blajchman ◽  
M R Buchanan ◽  
E A Johnson
Keyword(s):  
Vessel Wall ◽  
Dermatan Sulfate ◽  
Heparin Cofactor Ii ◽  
Thrombin Inhibition ◽  
Antithrombotic Effects ◽  
The Relationship ◽  
Functional Attribute ◽  
Prothrombin Activation

Studies have shown that dermatan sulfate (DS), heparan sulfate (HS) and chondroitin-4-sulfate (C4S), have antithrombotic properties. The sulfate to carboxylate ratios of these three glycosaminoglycans (GAGs) are approximately half that of heparin (HEP) and the gravimetric dose of each of the three GAGs required to achieve antithrombotic effects in vivo comparable to HEP can be 10 times or more than that of HEPT Since antithrombotic effects depend on the ability of a GAG to catalyse thrombin inhibition and/or to inhibit prothrombin activation, we determined the relationship between the extent of sulfation of various GAGs and their effects on these two reactions in normal plasma. In addition to the three GAGs, DS, HS and C4S were resulfated in vitro to yield DS-S, HS-S and C4S-S, each with a sulfate to carboxylate ratio comparable to that of heparin. As summarized below, increased sulfation improved the ability of a GAG to catalyse thrombin inhibition and to inhibit prothrombin activation. Increasing the degree of sulfation primarily improved the ability of a GAG to accelerate the inhibition of thrombin by heparin cofactor II. The degree of sulfation, therefore, appears to be an important functional attribute of the ability of vessel wall GAGs to regulate the formation and activity of thrombin in plasma.

scholarly journals Sulfated polysaccharide from the red algae Gelidiella acerosa: Anticoagulant, antiplatelet and antithrombotic effects

2020 ◽  
Vol 159 ◽  
pp. 415-421 ◽  
Author(s):  
Francisco Diêgo da Silva Chagas ◽  
Glauber Cruz Lima ◽  
Valesca Ingrid Nobre dos Santos ◽  
Luís Eduardo Castanheira Costa ◽  
Willer Malta de Sousa ◽  
...  
Keyword(s):  
Red Algae ◽  
Sulfated Polysaccharide ◽  
Gelidiella Acerosa ◽  
Antithrombotic Effects

Further Studies on the Mechanism for the Antithrombotic Effects of Naroparcil, an Orally Active Thioxyloside Compound

1999 ◽  
Vol 81 (06) ◽  
pp. 945-950 ◽  
Author(s):  
J. Theveniau ◽  
D. Coup ◽  
T. Grégoire ◽  
M. Vaillot ◽  
D. Dupouy ◽  
...  
Keyword(s):  
Specific Activity ◽  
Heparin Cofactor Ii ◽  
Antithrombotic Activity ◽  
Thrombin Inhibition ◽  
High Affinity ◽  
Antithrombotic Effects ◽  
Orally Active ◽  
The Relationship ◽  
In Vitro Specific Activity

SummaryThe antithrombotic β-D-xyloside, naroparcil, has previously been shown to induce a dose-related increase of circulating glycosaminoglycans (GAGs) together with an antithrombin activity (anti-IIa) via heparin cofactor II (HCII) in the rabbit. In order to go further in the mechanisms, the relationship between the antithrombotic activity, the HCII-mediated anti-IIa activity and the plasma GAG content was investigated. We showed that the in vitro specific activity on the inhibition of thrombin by HCII of the plasma GAG extract from naroparcil-treated rabbits was increased by a factor of 60 when compared to controls. In addition, the fractionation of the plasma GAG extract by affinity chromatography on immobilized HCII led to a more potent material whereas the low-affinity fraction was shown to be inactive in thrombin inhibition by HCII.The qualitative analysis of GAGs showed the presence of the ΔDi-4S DS disaccharide, undetectable in control, which accounted for 22% in the unfractionated GAG extract and for 60% in the high affinity fraction. In vitro experiments using immuno-depleted plasma in antithrombin III (ATIII), HCII or both, indicated that the anti-IIa activity of the plasma GAG extract from naroparcil-treated rabbits was mainly due to HCII potentialisation. The unfractionated GAG extract and the high affinity fraction were shown to be antithrombotic in a Wessler-based model in the rat, giving ED80 values of 610 UA/kg and 56 UA/kg respectively whereas the low-affinity fraction was devoid of any antithrombotic activity. These results show that the antithrombotic activity of naroparcil is dependent on modification in the plasma GAG profile which inactivates thrombin via the HCII.

scholarly journals Biological Activities of Rhamnan Sulfate Extract from the Green Algae Monostroma nitidum (Hitoegusa)

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 228 ◽  
Author(s):  
Koji Suzuki ◽  
Masahiro Terasawa
Keyword(s):  
Vascular Dysfunction ◽  
Biological Activities ◽  
Human Subjects ◽  
Biological Properties ◽  
Sulfated Polysaccharide ◽  
In Vivo Studies ◽  
Monostroma Nitidum ◽  
Antithrombotic Effects

Monostroma nitidum is a green single-cell layered algae that grows on the southwest coast of Japan. It is often used for salad ingredients, boiled tsukudani, soups, etc., due to its health benefits. M. nitidum is composed of many cell aggregates, and the various substances that fill the intercellular space are dietary fibers, vitamins, and minerals. Rhamnan sulfate (RS), a sulfated polysaccharide, is main the component of the fiber extracted from M. nitidum. Recently, some biological properties of RS have been demonstrated by in vitro and in vivo studies that probably protect human subjects from viruses and ameliorate vascular dysfunction caused by metabolic disorders, especially lifestyle-related diseases. In this review, we focus on the antithrombotic effects of RS and introduce its antiviral and other biological activities.

Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2

2020 ◽  
Vol 11 (9) ◽  
pp. 7415-7420 ◽  
Author(s):  
Shuang Song ◽  
Haoran Peng ◽  
Qingling Wang ◽  
Zhengqi Liu ◽  
Xiuping Dong ◽  
...  
Keyword(s):  
Red Algae ◽  
Brown Algae ◽  
Sea Cucumber ◽  
Sulfated Polysaccharide ◽  
Sulfated Polysaccharides ◽  
Inhibitory Activities

Sulfated polysaccharide from sea cucumber (SCSP), fucoidan from brown algae, and iota-carrageenan from red algae show inhibitory activities against SARS-CoV-2.

scholarly journals Chemical Structure and Anticoagulant Property of a Novel Sulfated Polysaccharide from the Green Alga Cladophora oligoclada

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 554
Author(s):  
Meijia He ◽  
Yajing Yang ◽  
Zhuling Shao ◽  
Junyan Zhang ◽  
Changning Feng ◽  
...  
Keyword(s):  
Green Alga ◽  
Coagulation Factors ◽  
Sulfated Polysaccharide ◽  
Marine Macroalgae ◽  
Sulfated Polysaccharides ◽  
Thrombin Time ◽  
Chemical Structures ◽  
At Iii

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)-β-d-Galp-(1→, β-d-Galp-(1→, →6)-α-d-Glcp-(1→ and →3)-β-d-Galp-(1→ units with sulfate esters at C-2/C-4 of →6)-β-d-Galp-(1→, C-6 of →3)-β-d-Galp-(1→ and C-3 of →6)-α-d-Glcp-(1→ units. The branches consisting of β-d-Galp-(1→ and →6)-β-d-Galp-(1→ units were located in C-3 of →6)-β-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.

Pharmacological Effects of a Novel Recombinant Hirudin, CX-397, In Vivo and In Vitro: Comparison with Recombinant Hirudin Variant-1, Heparin, and Argatroban

1999 ◽  
Vol 81 (02) ◽  
pp. 250-255 ◽  
Author(s):  
Yoshifumi Inoue ◽  
Yuso Goto ◽  
Tominaga Fukazawa ◽  
Hideya Hayashi ◽  
Yasuhiko Komatsu
Keyword(s):  
Arterial Thrombosis ◽  
Recombinant Hirudin ◽  
Dominant Type ◽  
Thrombin Inhibition ◽  
Venous Shunt ◽  
Antithrombotic Effects ◽  
Hemorrhagic Risk ◽  
Effective Doses

SummaryThe novel recombinant hirudin analog CX-397 was investigated with respect to its pharmacological activity and antithrombin profiles in vivo and in vitro. In three different types of thrombosis models in rats, including stasis and thrombin-induced venous, glass surface-activated arterio-venous shunt, and ferric chloride-induced arterial thrombosis models, CX-397 and rHV-1 elicited potent antithrombotic effects, where the minimum effective doses of rHV-1 tended to be higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis models. The hemorrhagic risk of CX-397 in template bleeding in rats was not higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for treating the platelet-dominant type of thrombosis. However, no differences were detected between CX-397 and rHV-1 in their effects on in vitro coagulation times and thrombin-induced platelet aggregation, suggesting the possibility that some unknown mechanisms other than simple thrombin inhibition are also involved in their anti-thrombotic actions.

scholarly journals Carrageenans as Broad-Spectrum Microbicides: Current Status and Challenges

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 435
Author(s):  
Choongho Lee
Keyword(s):  
Broad Spectrum ◽  
Red Algae ◽  
Viral Infections ◽  
Ex Vivo ◽  
Antimicrobial Activities ◽  
Current Status ◽  
Sulfated Polysaccharides ◽  
Future Research

Different kinds of red algae are enriched with chemically diverse carbohydrates. In particular, a group of sulfated polysaccharides, which were isolated from the cell walls of red algae, gained a large amount of attention due to their broad-spectrum antimicrobial activities. Within that group, carrageenans (CGs) were expected to be the first clinically applicable microbicides that could prevent various viral infections due to their superior antiviral potency and desirable safety profiles in subclinical studies. However, their anticipated beneficial effects could not be validated in human studies. To assess the value of a second attempt at pharmacologically developing CGs as a new class of preventive microbicides, all preclinical and clinical development processes of CG-based microbicides need to be thoroughly re-evaluated. In this review, the in vitro toxicities; in vivo safety profiles; and in vitro, ex vivo, and in vivo antiviral activities of CGs are summarized according to the study volume of their target viruses, which include human immunodeficiency virus, herpesviruses, respiratory viruses, human papillomavirus, dengue virus, and other viruses along with a description of their antiviral modes of action and development of antiviral resistance. This evaluation of the strengths and weaknesses of CGs will help provide future research directions that may lead to the successful development of CG-based antimicrobial prophylactics.

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