Antiplatelet and anticoagulant effects of diterpenes isolated from the marine alga, Dictyota menstrualis.

Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines.

Inhibitory effect of a Brazilian marine brown alga Spatoglossum schröederi on biological activities of Lachesis muta snake venom

The ability of crude extracts of the brown seaweed Spatoglossum schröederi to counteract some of the biological activities of Lachesis muta snake venom was evaluated. In vitro assays showed that only the extract of S. schröederi prepared in ethyl acetate was able to inhibit the clotting of fibrinogen induced by L. muta venom. On the other hand, all extracts were able to inhibit partially the hemolysis caused by venom and those prepared in dichloromethane or ethyl acetate fully neutralized the proteolysis and hemorrhage produced by the venom. Moreover, the dichloromethane or ethyl acetate extracts inhibited the hemolysis induced by an isolated phospholipase A2 from L. muta venom, called LM-PLA2-I. In contrast, the hexane extract failed to protect mice from hemorrhage or to inhibit proteolysis and clotting. These results show that the polarity of the solvent used to prepare the extracts of S. schröederi algae influenced the potency of the inhibitory effect of the biological activities induced by L. muta venom. Thus, the seaweed S. schröederi may be a promising source of natural inhibitors of the enzymes involved in biological activities of L. muta venom.

Allelopathic potential of extracts the from marine macroalga Plocamium brasiliense and their effects on pasture weed

Four extracts from the marine red alga Plocamium brasiliense (Greville) M.A.Howe & W.R.Taylor were prepared to identify and characterize their potential allelopathic effects on seed germination, radicle elongation and hypocotyl development of the weeds Mimosa pudica L. and Senna obtusifolia (L.) Irwin & Barneby. The four extracts were prepared in a sequence of solvents of increasing polarity: n-hexane, dichloromethane, ethyl acetate and ethanol/water (7:3). The germination bioassay was carried out at 25 °C with a 12 h photoperiod and the radicle elongation and hypocotyl development at 25 °C with a 24 h photoperiod. The dichloromethane extract showed inhibitory effects on seed germination of both plants (35 and 14%, respectively, in M. pudica and S. obtusifolia), radical germination (52 and 41.7%, respectively) and hypocotyl development (17.1 and 25.5%, respectively). Given the high sensitivity of this parameter to the potential allelopathic effects and the insufficient number of references found in the literature, these results are expected to stimulate new tests with other species of marine algae. Given the high sensitivity of the method for the detection of allelopathic potential, the species P. brasiliense emerges as a possible source of allelopathic substances against weed species. The results are attributed to the chemical composition, especially in relation to the presence of halogenated monoterpenes.

Evaluation of Marine Brown Algae and Sponges from Brazil as Anticoagulant and Antiplatelet Products.

The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders.