NATURAL DRUGS

Author: YÁÑEZ JATO MATILDE.
Year: 2004.
University: SANTIAGO DE COMPOSTELA [www.usc.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FARMACIA.

Summary: Garlic (Allium sativum L.) is one of the best known medicinal plants and studied. Its effect on the cardiovascular system is perhaps one of the most extensively documented in the scientific literature. Although his power therapeutic seems obvious, its mechanism of action is not known accurately and there are many studies that appear constantly trying to clarify. The study results are hardly uniform and sometimes contradictory due to the different methodologies used and the variability in the experimental conditions. Much of the observed differences are due to the wide range of formulas used garlic, which vary significantly the concentration of active compounds. Therefore, in this paper we evaluated independently effects and mechanisms of action on blood platelets and vascular smooth muscle cells of four compounds characteristic of this plant, but are not found in naturally occurring rapidly after his crushing: alicina, ajoene, disulfide díalilo and disulfide dipropilo. The alicina and ajoene, in a concentration range 1-25 UM And disulfide dialilo and disulfide dipropilo in the range 50-500 1UMbloquean completely aggregated action of collagen, while showing a dependent inhibitory effect of compared with thrombin concentration or ionomicina. When using a concentration 500 UMde disulfide dialilo there is a big increase in cytosolic calcium concentration, which causes the formation of microvesículas platelet. With a concentration 100 UMde disulfide dipropilo causes activation of phospholipase C, which leads to activation of platelets resulting in aggregation. In assessing the effect of alicina and ajoene on different points in the process of platelet activation and biochemical processes associated found as follows: - The concentrations of alicina and ajoene inhibiting platelet aggregation modified to varying degrees both spontaneous accession platelets, as induced by various agonists (mainly thrombin and collagen). - The alicina and ajoene, the concentrations studied, do not affect platelet shape change. - Both compounds, alicina and ajoene, inhibit secretion induced by thrombin 0.25 U / I, resulting effective ajoene, with an IC50 close to 5 UM.Este effect is related to the activity antiaggregatory shown by these substances. - The alicina and inhibit ajoene, so dependent on the concentration used, the increase in cytosolic calcium levels caused by the stimulation of platelet with thrombin. The increase induced by ionomicina not affected by the alicina while the ajoene caused a slight enhancement of the same. - Ajoene increases nearly 25% of baseline platelet levels of cAMP and power by 50% this nucleotide levels in platelets in which stimulates adenilatociclasa. At the concentrations tested, the alicina does not significantly alter the platelet concentration of cAMP. The basal levels of cGMP are not changed as a result of alicina or ajoene. However, incubation of platelets with ajoene whose guanylate cyclase is stimulated, potentially increasing the nucleotide by 30%. - The alicina and ajoene produce an increase in the level of tyrosine phosphorylation in various platelet proteins. The phosphorylation is an irreversible effect remained after removing the compounds from the middle of platelet resuspension. - The effect antiaggregatory shown by the alicina and ajoene does not appear related to the increase in tyrosine phosphorylation in caused by these compounds, but rather a consequence of the combined effect of different processes (inhibition of the increase in cytosolic calcium, inhi 8 bición d 76 e e secretion, increased level of platelet cAMP). - The increase in the degree of phosphorylation of the platelet protein is more a result of the stimulation of platelet tyrosine kinases, which caused the inhibition of tyrosine phosphatases on. - The ability of the alicina and ajoene to increase in tyrosine phosphorylation of certain proteins platelet disappears in platelet suspensions incubated with b-mercaptoetanol due to the leverage effect of this compound on the platelet tyrosine phosphatases. It also studied the potential impact of these derivatives on the smooth muscle cells that form the blood tissue, observed an inhibition in the proliferation dependent on the time of incubation and the concentration of compound used. This inhibition may be mediated by an action on the cytosolic calcium homeostasis and the inhibition of phosphorylation of tyrosine residues in the p38 MAPK. The effect does not appear to be specific because the compounds are also able to inhibit the proliferation of tumor cells HeLa, which also caused a decrease in the level of tyrosine phosphorylation in certain proteins.

Author: GONZÁLEZ SANTIAGO MARIA PILAR.
Year: 2004.
University: GRANADA [www.ugr.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Cardiovascular diseases are the leading cause of death in the world. The oxidation of LDL lipoprotein seems to be involved in the processes of initiation and progression of atherosclerosis. The hidroxitirosol is a phenolic compound present in olive oil with a powerful antioxidant activity and important biological properties that suggest that may exert a protective effect on cardiovascular disease. The objectives of this thesis were deepening on cardiovascular effects produced by the hidroxitirosol in an experimental model of atherosclerosis induced by a diet rich in saturated fat and cholesterol in rabbits, studying absorption when it is ingested orally both animal and human and research on the possible mechanisms of action involved through the study of their association with the human plasma lipoproteins and their effect on gene expression in mouse liver using microarray technology. The daily administration of 4 mg / kg hidroxitirosol pure rabbits ateroscleróticos resulted in a significant reduction of 42% and 48% in the plasma concentrations of total cholesterol and triglycerides, respectively, doubled the concentration of cholesterol in plasma, fell to lipid peroxidation measured as malondialdehyde and increase the antioxidant capacity of plasma. It also produced a minor breakthrough in the atherosclerotic lesion, measured as intimate area of the layer in the aortic cayado, which was significantly reduced in the experimental groups that received hidroxitirosol. When hidroxitirosol purified was dissolved in water and administered fasting, introduced a maximum plasma concentration of 10 minutes in rats and 13 minutes in human and then declined rapidly concentration. Metabolites from hidroxitirosol found were alcohol homovanílico, acid homovanílico and acid dihidroxifenilacético, all of them with antioxidant activity, which in humans were excreted in urine as free or with glucuronide and sulfate conjugates. The hidroxitirosol showed in human plasma by affinity specific lipoprotein LDL. This union was able transient and was not found for the remainder of the metabolites from hidroxitirosol. The administration of 0.05 and 0.5 g / kg hidroxitirosol for 15 days to healthy mice produced weak effects on the expression of genes involved in the synthesis of cholesterol, lipid metabolism and glucídico, inflammation, blood clotting, angiogenesis and contraction smooth muscle in mouse liver.

Author: OLMOS FONT ANA.
Year: 2005.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: In this paper deals with the study of the effect on the nitración tyrosine produce hydroquinone and two derivatives cafeicos isolated Phagnalon rock (Asteraceae). Analysis has been made in tyrosine free and bovine albumin. In both trials gives a prominent activity for the compounds under study. When nitración carried out by peroxynitrite, the effect of the compounds is affected by the presence of bicarbonate, in contrast to the results obtained when the nitración is made with nitrite, catalysed by the system hemoproteínas. Based on spectroscopic data shows that the 1-glucosil-2-isoprenilhidroquinona inhibits nitración tyrosine by peroxynitrite by forming a derivative 5-mononitrado however, the methyl ester acid 3,5-dicafeilquínico is very sensitive to oxidation and resistant to nitración. In determining nitración intracellular fibroblasts, the compounds must be present in the medium when added peroxynitrite, thereby blocking the rapid progression of their effects. When using human polymorphonuclear leukocytes stimulated by acetate miristoílforbol get too high powers to the three principles, especially for derivatives cafeicos. Finally, we evaluated the effect of the compounds on the modeling of contact hypersensitivity induced oxazolona and dinitrofluorobenceno in mice, including those relating to the genesis of NO and derivatives nitrantes. Esters cafeicos presented, in general, an antiinflammatory effect than the hydroquinone, both on the handset thickness as on the release of cytokines.

Author: ZENG YUEQIN.
Year: 2005.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: This Doctoral Thesis has focused on the study of species used in traditional Chinese medicine and other species used in folk medicine as an anti-inflammatory, particularly in processes that affect the skin. The species under study were Schinus molle, Lysimachia foenum - graecum, Lithospermum erythrorhizon, Forsythia suspensa and Isodon xerophilus. The experimental development has been prefetching of plant material through appropriate means, in each case, extraction and fractionation of the extracts. Study analytical and pharmacological all extracts obtained and isolation and identification of the major principles of the active fractions. As in vivo experimental methods have been developed protocols for acute and chronic inflammation in the ear of mouse induced by 13-acetato of 12-O-tetradecanoilforbol (TPA) and the models of acute edema foot mouse and carrageenan-induced phospholipase A2 (PLA2). Among the techniques developed in vitro include the identification of cytotoxicity, inhibition of the production of nitrite, leukotriene B4 and mediators peptídicos in isolated cells, as well as antioxidant activity. Among the most visible results will include a) isolation of two triterpenes and biflavanona extract diclorometánico of Schinus molle and determination of the activity antiiflamatoria b) isolation of five new saponósidos of Lysimachia foenum - graecum and study of their cytotoxicity and ability inhibition of the production of leukotriene B4 c) determination of the antioxidant activity of extracts of Lithospermum erythrorhizon and principles present in the same d) isolation of two anti-inflammatory extract triterpenes of Forsythia suspensa and determination of the antioxidant activity of the fractions obtained e), and finally the isolation of 14 diterpenoides of Isodon xerophilus and determination of cytotoxicity, inhibition of nitric oxide production and inhibiting the production of TNF.

Author: AMIGÓ AVELLÁN MARÍA.
Year: 2006.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: In this paper, it has assessed the impact of a number of derivatives of avarol on various parameters involved in the development of psoriasis, both at the level of cell proliferation and differentiation of keratinocytes, and at the level of inflammatory component of this disease. In a preliminary screening, has studied the antioxidant activity of the compounds in human neutrophils. The cell line of human HaCaT we keratinocytes determined the effect of derivatives on the generation of PGE2 and on cell proliferation. In human keratinocytes has been evaluated to be able to regulate differentiation markers psoriatic (SAKLP / Elafín) and differentiation of normal (citoqueratina 10), as well as the effect of derivatives on the proliferation. Following the completion of this preliminary screening has been selected derivative tiosalicílico of avarol for its potent antioxidant activity and inhibition of the generation of PGE2. In addition, this compound inhibits the activation of NF-? B in keratinocyte HaCaT stimulated with TNF. In a parallel study, has studied the effect fotoprotector derivative tiosalicílico of avarol and a series of 13 new derivatives tioavarol compared to UVB irradiation in keratinocyte HaCaT. The results highlight of the new derivative tiosalicílico of avarol to reduce TNF-ay activation NF-? B after radiate with UVB. The derivative tiosalicílico reduces concentration-dependent manner in the production of PGE2 and TNF-stimulated human monocytes, as well as the generation of LTB4 in human neutrophils. This compound inhibits the activity sPLA2 determined in a cell free system and in the supernatant keratinocyte HaCaT. In the model of an airbag in mice induced zimosán, derivative tiosalicílico produces a dose-dependent decrease all certain parameters (PGE2, LTB4, TNFa) in drips after 4 h after injection of zimosán. In the model of TPA-induced hyperplasia in mouse skin, topical application of derivative avarol reduces swelling, and mieloperoxidasa activity levels eicosanoides. The histochemical study shows that decreases leukocyte infiltration and epidermal hyperplasia, as well as the levels of TNF-as has been observed in an immunohistochemical analysis. This compound also inhibits nuclear translocation of NF-? B determined in vivo in mouse skin.