Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.
"Derivatives of Pec methacrylated (Souto-Maior, Reis, Pedreiro, & Cavalcanti, 2010), amidated (Mishra, Datt, Pal, & Banthia, 2008), thiolated (Perera, Hombach, & Bernkop-Schnurch, 2010), and sulfated (Cipriani et al., 2009) which have already been obtained and studied. Among these, the methacrylated derivative of Pec receives greater attention since it can be polymerized and then used to prepare biodegradable hydrogels for application in biomaterial field (Oh, Lee, & Park, 2009). "
[Show abstract][Hide abstract] ABSTRACT: New pectin derivative (Pec-MA) was obtained in specific reaction conditions. The presence of maleoyl groups in Pec-MA structure was confirmed by 1H NMR and FTIR spectroscopy. The substitution degree of Pec-MA (DS = 24%) was determined by 1H NMR. The properties of Pec-MA were investigated through WAXS, TGA/DTG, SEM and zeta potential techniques. The Pec-MA presented amorphous characteristics and higher-thermal stability compared to raw pectin (Pec). In addition, considerable morphological differences between Pec-MA and Pec were observed by SEM. The cytotoxic effect on the Caco-2 cells showed that the Pec-MA significantly inhibited the growth of colon cancer cells whereas the Pec-MA does not show any cytotoxic effect on the VERO healthy cells. This result opens new perspectives for the manufacture of biomaterials based on Pec with anti-tumor properties.
"Chemical sulfation of polysaccharides is one of the most utilized procedures to produce heparin analogs. This type of chemical modification is reproducible and allows the employing of high amounts of polysaccharides obtained from renewable non-animal sources (Cipriani et al., 2009; Papy-Garcia et al., 2005). Regioselective sulfation approaches have been introduced to synthesize polysaccharides with defined sulfation patterns, and in association with biological activity studies, the best sulfate positioning have been identified (Groth & Wagenknecht, 2001; Peschel, Zhang, Fischer, & Groth, 2012). "
[Show abstract][Hide abstract] ABSTRACT: Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-d-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-d-Galp and C6 of β-d-Galp increased the anticoagulant activity.
[Show abstract][Hide abstract] ABSTRACT: The leaf decoction of Croton zambesicus Müell. Arg. (Euphorbiaceae; syn. Croton amabilis Müell. Arg., Croton gratissimus Burch) is traditionally used in Benin to treat hypertension.
As hypertension and thromboembolism are often associated in several cardiovascular diseases, we studied the potential effects of leaf extracts from Croton zambesicus on hemostasis.
We prepared the dichloromethane and aqueous extracts from the air-dried leaves of Croton zambesicus and separated the aqueous extract in its aqueous and dichloromethane fractions. The potential effects of these four extracts/fractions were investigated on red blood cells integrity using spectrophotometric lysis assays, on primary hemostasis using platelet aggregation studies and on secondary hemostasis using calibrated automated thrombin generation assays and coagulation factors inhibition tests.
In the in vitro testing, we found that none of the tested extracts/fractions exhibit hemolytic or antiplatelet activity. However, they display a moderate but significant anticoagulant activity which would be mediated through the direct inhibition of thrombin, FXa and TF/FVIIa. The active anticoagulant compound(s) seem to be mainly in the aqueous extract and especially in its aqueous fraction.
This experimental work reported for the first time the anticoagulant effect of leaf extracts from Croton zambesicus. These findings are of particular interest as the leaves from Croton zambesicus are commonly used in infusion by local population and may provide a new natural source for the development of original anticoagulant agents. Furthermore, this activity, associated with the vasorelaxant properties of some of its diterpenes may prove to be interesting for the prevention of cardiovascular diseases in traditional medicine.
Journal of ethnopharmacology 02/2010; 128(3):641-8. DOI:10.1016/j.jep.2010.02.007 · 3.00 Impact Factor
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