PHARMACOPOEIAS

Author: NÚÑEZ PENAS FRANCISCO JAVIER.
Year: 2005.
University: SANTIAGO DE COMPOSTELA [www.usc.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: The fucanos are sulfated polysaccharides present in the intercellular matrix of brown algae (Phaeophyceae) and unions are formed by heterogeneous polymer. The main objective of this research has been to demonstrate the ability of fucanos present in the algae Cystoseira tamariscifolia and Laminaria ochroleuca to positively alter blood lipid levels in various experimental models, and explore its effect on lipoprotein lipase, one of the key enzymes in lipid metabolism. Also, to expand the study, a follow-up to its potential therapeutic potential on the physiological processes of platelet aggregation and blood clotting. Through the method of Mian and Percival were isolated extracts raw calcium and hydrochloric of both algae and then conducted its franccionamiento by gradient through an ion exchange chromatography using a column of DEAE-Sephacel. After this process four fractions were obtained from each of the extracts gross for the elution with potassium chloride concentration increased 0.15, 0.3 and 1 M. It was subsequently conducted a chemical characterization of fucanos extracted from seaweed, in order to link their chemical structure with their biological activity. This process included determining the content in sulphate groups, fucosa, urónicos acids and reducing sugars, determining the molecular weight, and conducting genetic corresponding infrared spectra. The chemical characterization of the fractions is a trend in these enriched in fucosa and impoverished in reducing sugars with increasing ion gradient elution. Just as, in general, the degree of sulfation of fractions increases in direct relation to the elution of ionic potential. The molecular weight determined by gel filtration chromatography on Sephacryl S-400 HR showed that L.ochroleuca presents more diverse fucanos that C.tamariscifolia and that fucanos of fractions of C.tamariscifolia are, in general, smaller than of L.ochroleuca. Then the fucanos underwent drug in a study that sought to determine their effects on blood lipid levels in different models lipemia. In rats normolipémicas, crude extracts isolated from the two species of algae have a powerful effect hipotriglíceridemiante dose dependent. The extract hydrochloric of C.tamariscifolia is the most active in this respect and, in addition, it also reduces a significant and dose-dependent levels of total cholesterol and LDL cholesterol. In rats with hyperlipidemia induced Tiloxapol, after the completion of preliminary testing, and testing phase and the second phase, it appears that the various crude extracts and fractions of the two algae have an important effect hiptriliceridemiante. The best results are offered fractions clorhídricas of C.tamariscifolia who are able to transform were highly opalescent (TG 600 mg / dl) in serum triglycerides with near-normalcy (TG 100 mg / dl). Of the different studies in rats with hyperlipidemia induced Tiloxapol also concludes that fucanos analyzed have a moderate effect hipocolesterolemiante mainly fractions clorhídricas of C.tamariscifolia expressing this effect by stimulating the process of elimination. The lipid lowering activity of the different fractions of an extract from the same algae is directly related to the content in groups and inversely with the sulfate content in reducing sugars. The comparative analysis of extracts crude fractions between the two algae concludes that the activity hipolipermiante is affected also by molecular weight, since a smaller implies greater activity. In trials on lipase activity, and the doses tested, all gross and extracts all fractions showed a potent stimulant dose dependent on the activity of lipoprotein lipase. Results from the fraction 8 ions 99th C.tamariscifolia remained consistent with the data of decreased plasma triglycerides in the trials of lipid. So, that the lipase activity rises to incrementares the degree of sulfation, and decreases with increasing molecular weight. To check whether the fucanos administered by intraperitoneal route occurring differences in absorption testing was conducted concentrations plasmáticas-tiempo which showed that the differences in biological activity between fucanos are not due to differences in bioavailability. The affinity chromatography on Heparin-Sepharosa demonstrated the existence of an ionic interaction between different fucanos studied and the enzyme lipoprotein lipase, with a directly proportional relationship between the content in groups sulfate polysaccharides and their affinity for lipoprotein lipase in column . Moreover, when the degree of sulfation is similar, fucanos lower molecular weight are the ones who move more actively to the enzyme from binding to heparin. The trials of platelet aggregation with seaweed C.tamariscifolia showed that the fractions 0.5 and 1 M of both crude extracts and the fraction 0.15 M clorhídrica presented antiaggregatory action which is directly related to the content in sulphate groups and inversely with the molecular weight. Different tests coagulation (TT, TP and APTT) have revealed the expected anticoagulant effect of fucanos these brown algae, interacting directly with the activity content in sulphate groups but has not been found relationship actividad-peso molecular level. As final conclusion, we must emphasize that the fucanos of fractions 0.5 and 1M clorhídricas of Cystoseira tarmariscifolia presented potentísima activity hipotrigliceridemiante, remarkable activity hipocolesterolemiante moderate antiaggregatory activated platelet activity and very slight anticoagulant that makes molecules with high potential for use in preventing the ischemic arterial disease.