Abstract
Caulerpa cupressoides produces sulfated polysaccharides (Cc-SPs) with serpin-dependent anticoagulant effect, but their actions on thrombin generation (TG) are unknown. This study aimed to partially characterize Cc-SPs and examine their potential as modulators of TG. Infrared analysis characterized extract containing three ulvan fractions (Cc-SP1, -SP2 and -SP3) separated by DEAE-cellulose chromatography, with differences in the relative proportions of sulfate (10.99-18.38%) and total sugars (46.59-51.12%), without presenting proteins. Charge density patterns and nonSPs varying from 8 to > 100 kDa on agarose and polyacrylamide gel electrophoresis by sequential staining with toluidine blue and stains-all were also confirmed by gel permeation chromatography. The molecular weight of Cc-SP2 was not altered after treatment with 0.4 M HCl up to 5 h. Only Cc-SP2 altered the activated partial thromboplastin time (15 ± 0.3 IU) vs. heparin (193 IU) and abolished at high concentrations (> 4.1 µg) TG by intrinsic pathway in 60-fold diluted human plasma, while at 4.1 µg attenuated TG by 33.87% delaying the lag phase (32 min.) vs. control (28 min.). Cc-SP2 induced concentration-dependent TG in system without cephalin. Heparin abolished TG at 4.15-fold lower amount, but did not stimulate TG. Therefore, Cc-SPs express dual effects on thrombosis in vitro.
Highlights
Cardiovascular diseases currently constitute the major global incidence of mortality and morbidity and the thromboembolic events arise in about one in 1,000 individuals per year, especially in the developed countries
It has been described that the structures of sulfated polysaccharides (SPs) produced by Chlorophyta belonging to the Bryopsidales galactans predominate (Wang et al, 2014; Arata et al, 2015)
Using fractions at different concentrations (4.1→83.3 μg well-plate-1) (Rodrigues et al, 2016; Salles et al, 2017; Rodrigues et al, 2017b), our results showed that sulfate differentially interfered with the thrombin generation (TG) response in 60-fold diluted human plasma activated by cephalin as recorded continually at 37°C for 60 min., in comparison with Unfractionated heparin (UHEP) used as a reference
Summary
Cardiovascular diseases currently constitute the major global incidence of mortality and morbidity and the thromboembolic events arise in about one in 1,000 individuals per year, especially in the developed countries. Seaweeds of the genus Caulerpa Lamouroux (1809) (Bryopsidales, Chlorophyta) comprise a green biomass overgrowing in eutrophicated waters generating environmental and economic impacts (Wang, Wang, Wu, & Liu, 2014) Opportunities to their use as food by coastal communities and human nutrition have been practiced in the Indo-Pacific region for centuries to reduce the risk of chronic diseases, such as neurodegenerative, inflammatory and cardiovascular complications, due to their substantial diversity of natural bioactive molecules with health benefits (Gaillande, Payri, Remoissenet, & Zubia, 2017) and as food ingredients (Kumar et al, 2018), besides Caulerpa cultivation on a large scale in Southeast Asia, such as C. lentillifera, where this species is popularly consumed and explored in therapeutic medical applications (Maeda, Ida, Ihara, & Sakamoto, 2012)
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