Tomás Adzet

Antifungal activity of Paraguayan plants used in traditional medicine

The antifungal activity of aqueous, dichloromethane and methanol extracts from 14 Paraguayan plants used in traditional medicine for the treatment of skin diseases was assayed in vitro by the agar disk diffusion method against 11 fungal strains comprising several filamentous fungi and yeasts. Among them, the dichloromethane extracts of Acanthospermum australe, Calycophyllum multiflorum, Geophila repens and Tabebuia avellanedae, as well as the aqueous and methanol extracts of the latter, showed the highest activity.

Heterotheca inuloides: Anti-inflammatory and analgesic effect

Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of Mexico. The aqueous extract obtained from the flowers of H. inuloides was assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100 mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1), butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous extract. The biological assay, by carrageenan-induced edema test, gave the following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2 was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal examination after the treatment with HI-2 showed that the anti-inflammatory action of H. inuloides was not due to an irritating effect at the injection site. At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1% inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg. The results showed related anti-inflammatory activity and the analgesic effect of HI-2.

Activity of artichoke leaf extract on reactive oxygen species in human leukocytes.

Artichoke leaf extract was studied in human leukocytes for activity against oxidative stress using flow cytometry and dichlorofluorescin diacetate as a fluorescence probe. It produces a concentration-dependent inhibition of oxidative stress when cells are stimulated with agents that generate reactive oxygen species (ROS): hydrogen peroxide, phorbol-12-myristate-13-acetate (PMA), and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Cynarin, caffeic acid, chlorogenic acid, and luteolin, constituents of artichoke leaf extract, also show a concentration-dependent inhibitory activity in the above models, contributing to the antioxidant activity of the extract in human neutrophils.

Essential oils from four piper species

Abstract The essential oils from Piper capense , P. nigrum , P. guineense and P. umbellatum from S. Tome e Principe were investigated for the first time. They were analysed by GC, GC-mass spectrometry and 13 C NMR. Monoterpene hydrocarbons were the main group of constituents in three of the samples ( P. capense, P. nigrum and P. umbellatum ), whereas for the other species ( P. guineense ) phenylpropanoid derivatives were the most important ones. β -Pinene (32.5%) and β -caryophyllene (12.6%) were the major compounds in the volatile oil of P. capense . Dillapiole (44.8%), followed by myristicin (9.8%), were the main constituents of P. guineense . The most important constituents in the essential oil of P. nigrum were limonene (18.8%), β -caryophyllene (15.4%), sabinene (16.5%) and β -pinene (10.7%). The essential oil of P. umbellatum was characterised by its high β -pinene (26.8%), α -pinene (17.6%) and (E)-nerolidol (12.4%) content.

Increased reactive oxygen species production down-regulates peroxisome proliferator-activated alpha pathway in C2C12 skeletal muscle cells.

Generation of reactive oxygen species may contribute to the pathogenesis of diseases involving intracellular lipid accumulation. To explore the mechanisms leading to these pathologies we tested the effects of etomoxir, an inhibitor of carnitine palmitoyltransferase I which contains a fatty acid-derived structure, in C2C12 skeletal muscle cells. Etomoxir treatment for 24 h resulted in a down-regulation of peroxisome proliferator-activated receptor α (PPARα) mRNA expression, achieving an 87% reduction at 80 μm etomoxir. The mRNA levels of most of the PPARα target genes studied were reduced at 100 μm etomoxir. By using several inhibitors of de novo ceramide synthesis and C2-ceramide we showed that they were not involved in the effects of etomoxir. Interestingly, the addition of triacsin C, a potent inhibitor of acyl-CoA synthetase, to etomoxir-treated C2C12 skeletal muscle cells did not prevent the down-regulation in PPARα mRNA levels, suggesting that the active form of the drug, etomoxir-CoA, was not involved. Given that saturated fatty acids may generate reactive oxygen species (ROS), we determined whether the addition of etomoxir resulted in ROS generation. Etomoxir increased ROS production and the activity of the well known redox transcription factor NF-κB. In the presence of the pyrrolidine dithiocarbamate, a potent antioxidant and inhibitor of NF-κB activity, etomoxir did not down-regulate PPARα mRNA in C2C12 skeletal muscle cells. These results indicate that ROS generation and NF-κB activation are responsible for the down-regulation of PPARα and may provide a new mechanism by which intracellular lipid accumulation occurs in skeletal muscle cells.

Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits

The effects of atorvastatin (3 mg kg−1) and simvastatin (3 mg kg−1) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits. Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of feeding. Treatment with statins during the last 4 weeks of feeding abolished the progression of hypercholesterolaemia and reduced plasma triglyceride levels. 3‐Hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, acyl‐coenzyme A:cholesterol acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities were not affected by drug treatment. Accordingly, hepatic free cholesterol, cholesteryl ester and triglyceride content were not modified. Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity. Atorvastatin caused a reduction in hepatic phospholipid content and a compensatory increase in CTP:phosphocholine cytidylyl transferase activity. The results presented in this study suggest that, besides the inhibitory effect on 3‐hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, simvastatin and atorvastatin may have additional effects that contribute to their triglyceride‐lowering ability.

Screening for antifungal activity of nineteen Latin American plants

Dichloromethane and methanol extracts of 19 Latin American plants, most of them selected on the basis of traditional medicine reports, were subjected to screening for antifungal activity, using the agar disk diffusion assay against several fungi. Of the extracts tested, those of Andira inermis, Andira surinamensis, Bixa orellana, Blepharocalyx tweediei, Croton zehtneri, Gallesia integrifolia, Hedyosmum anisodorum, Heterotheca inuloides, Hura crepitans, Mansoa alliacea, Ocimum micranthum, Persea laevigata, Piper elongatum, Piper fulvescens, Polygonum hydropiperoides and Potalia amara exhibited some level of activity.

Chemical polymorphism of the essential oil of Thymus carnosus from portugal

Abstract The composition of the essential oils of 11 populations of Thymus carnosus from Portugal and their infraspecific variability were investigated by GC, GC-MS and 13CNMR. The results obtained were submitted to Principal Component and Chemometric Cluster Analyses. Borneol was the main constituent in all the populations except in one, which had a high content of linalool. This compound showed high percentages in samples originating from the region of Estremadura. Multivariate analysis allowed the distinction between three different groups of essential oils, (i) borneol/cis-sabinene hydrate/terpinen-4-ol, (ii) linalool/borneol/trans-sabinene hydrate and (iii) borneol/camphene.

High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production

Treatments with high doses of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors may induce the expression of sterol regulatory element binding protein (SREBP)-target genes, causing different effects from those attributed to the reduction of hepatic cholesterol content. The aim of this study was to investigate the effects of high doses of statins on the key enzymes involved in VLDL production in normolipidemic rats. To examine whether the effects caused by statin treatment are a consequence of HMG-CoA reductase inhibition, we tested the effect of atorvastation on these enzymes in mevalonatefed rats. Atorvastatin and simvastatin enhanced not only HMG-CoA reductase but also the expression of the SREBP-2 gene itself. As a result of the overexpression of SREBP-2 caused by the statin treatment, genes regulated basically by SREBP-1, as FA synthase and acetyl-coenzyme A carboxylase, were also induced and their mRNA levels increased. DAG acyltransferase and microsomal IG transfer protein mRNA levels as well as phosphatidate phosphohydrolase activity were increased by both statins. Simvastatin raised liver cholesterol content, ACAT mRNA levles, and CTP:phosphocholine cytidylyltransferase activity, whereas it reduced liver DAG and phospholipid content. Mevalonate feeding reversed all changes induced by the atorvastatin treatment. These results show that treatment with high doses of statins induces key enzymes controlling rat liver lipid synthesis and VLDL assembly, probably as a result of SREBP-2 overexpression. Despite the induction of the key enzymes involved in VLDL production, both statins markedly reduced plasma TG levels, suggesting that different mechanisms may be involved in the hypotriglyceridemic effect of statins at high or low doses.

Variability of essential oils of Thymus caespititius from portugal

Abstract The composition and variability of the essential oils of several populations of Thymus caespititius from Portugal were investigated by GC, GC-mass spectrometry and 13 C NMR. All samples from NW Portugal were characterized by their high α-terpineol content, while the main components in the oil sample from Pico island (Azores archipelago) were carvacrol and thymol. The analytical data of individual samples from NW Portugal showed no chemical polymorphism in this area. The different areas of distribution (NW Portugal and Azores) that show great climatic and soil variation conditions may be the origin of the α-terpineol-type oil from NW Portugal and the carvacrol/thymol-type oil from the Azores. 13 C NMR spectra of the essential oil, previously fractionated by column chromatography, led to the identification of trans -dihydroagarofuran, a new oxygenated sesquiterpene for the genus Thymus and a characteristic compound of T.caespitiuius .