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Fil: Martino, Renzo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Martino, Renzo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciónes Biomédicas; Argentina Fil: Barreiro Arcos, María Laura. Consejo de Investigaciones Científicas y Técnica; Argentina Fil: Peralta, Ignacio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Peralta, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marrassini, Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Marrassini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Saint Martin, Elina Malén. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Saint Martin, Elina Malén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cogoi, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Cogoi, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciónes Biomédicas; Argentina Fil: Cremaschi, Graciela A. Consejo de Investigaciones Científicas y Técnica; Argentina Fil: Alonso, María Rosario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Alonso, María Rosario. Consejo de Investigaciones Científicas y Técnica; Argentina Fil: Anesini, Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Fil: Anesini, Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de la Química y Metabolismo del Fármaco; Argentina Abstract: Most of the deaths from skin cancer are caused by melanoma, a malignancy in which STAT3 plays a crucial role. The inhibition of STAT3 is considered a potential target to induce cell death, tumor regression and metastasis inhibition. The objective of this work was to evaluate the activity of the aqueous extract of Larrea divaricata (Aq), a fraction rich in polyphenols (EA),and the isolated compound quercetin-3-methyl ether (Q3ME) on B16F10 melanoma cells. The effects of Aq, EA and Q3ME were assessed on B16F10 cells by determining the proliferation, viability, apoptosis induction and the expression and phosphorylation of STAT3. The phytochemical composition of the extracts was determined by High Performance Liquid Chromatography. Aq, EA and Q3ME presented antiproliferative activity on B6F10 cells through p-STAT3 inhibition and early and late apoptosis induction (EC50 EA= ≤0.1 μg/ml; Aq= 316±30 μg/ml; Q3ME=

Background: Urera aurantiaca is an Argentinean species that has been traditionally used to treat symptoms of inflammation. The aim of this study was to determine and compare the anti-inflammatory and antioxidant effects of two specimens of Urera aurantiaca obtained in the provinces of Salta and Misiones, which are two different geographical areas of Argentina. Methods: The anti-inflammatory activity of the extracts was tested in LPS-stimulated macrophages through the DPPH radical scavenging activity, the SOD-like activity, the reducing power and the inhibition of lipid peroxidation. The anti-inflammatory activity was also evaluated by the inhibition of albumin denaturation and proteinase inhibitory action tests. The total polyphenols, flavonoids and tannins content were quantified. Results: Both extracts were able to reduce the augmented NO release in LPS-activated macrophages and showed antioxidant and in vitro anti-inflammatory activities. The polyphenols content was higher in the extract obtained from the specimen from Salta than in that obtained in Misiones. This finding accounts for the higher anti-inflammatory and antioxidant properties obtained with the former. Conclusion: The differences in chemical composition and the biological activities observed between the extracts are probably related to the different environmental conditions found in both provinces. Fil: Marrassini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Peralta, Ignacio Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Anesini, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

Larrea divaricata Cav. (Zygophyllaceae) is a South American plant widely distributed in Argentina that is used in folk medicine to treat inflammatory diseases. The aqueous extract is known to have well-documented biological activities such as antitumour, immunomodulatory, antimicrobial, antiinflammatory and antioxidant. However, its stability in gastrointestinal fluids is unknown. The latter is an important factor to assure the bioavailability of plant extracts intended to be administered via the oral route. The aim of this work was to study the stability of a lyophilized aqueous extract of L. divaricata compressed as a pill. To this end, the main polyphenol compound found in the extract, that is, the nordihydroguaiaretic acid, the total polyphenols and flavonoids content and the antioxidant activity such as diphenylpicrylhydrazyl scavenger activity and reducing power were assayed after subjecting the extract to different incubation times in simulated digestive fluids. The HPLC and spectroscopic methods were employed. Although the levels of polyphenols and flavonoids decreased upon incubation in gastric and intestinal fluids, the extract maintained its antioxidant activity related to the presence of nordihydroguaiaretic acid. These results are promising and encourage the potential use of the extract by the oral route as a supplement or phytomedicine with antioxidant activity. Copyright © 2017 John Wiley & Sons, Ltd.

Background: Oxidative stress is an imbalance between the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS) and endogenous antioxidants. The aetiology and pathogenesis of several oral diseases are attributed to this process. The antioxidant enzymes secreted in the saliva by submandibular glands maintain oral health through the scavenging of ROS. The objective of this work was to study the capacity of an aqueous extract of L. divaricata (AE), and its majority compound, nordihydroguariaretic acid (NDGA), to modulate the pro-oxidant/antioxidant status in submandibular glands in a model of oxidative stress induced by streptozotocin (STZ) in rats. Methods: To induce oxidative stress with STZ, a group of animals was treated i.p. with 1 X PBS (control group) and other group was injected i.p. once with STZ (60 mg/kg). Ten days after the treatment, blood samples were taken from the tail vain to determine the glucose levels. Animals with glucose values ≥300 mg/ml were selected. The submandibular glands of control and STZ treated animals were incubated with either the AE (500 μg/ml) or with NDGA (1.5 μg/ml), and the content of malondialdehyde (MDA), protein carbonyl groups, ROS and RNS, and the activity and expression of peroxidase (Px), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) were assayed. Results: AE decreased the levels of MDA (## P < 0.01) and protein carbonyl groups (# P < 0.05), and modulated the levels of ROS such as hydrogen peroxide (H2O2)(##P < 0.01), superoxide anion (O2 .-) (# P < 0.05) and nitric oxide (NO) (# P < 0.05) in relation to the modulation of Px and iNOS expression. NDGA was found to be involved in these effects. Conclusions: The antioxidant activity of the AE in the submandibular glands would allow the maintenance of the antioxidant pool to prevent oral oxidative diseases. Fil: Peralta, Ignacio Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Marrassini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Alonso, María Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Anesini, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

A detailed study of biomaterials is mandatory to comprehend their feasible biomedical applications in terms of drug delivery and tissue regeneration. Particularly, mucoadhesive biopolymers such as chitosan (chi) and carboxymethylcellulose (CMC) have become interesting biomaterials regards to their biocompatibility and non-toxicity for oral mucosal drug delivery. In this work, pH-responsive biopolymer-silica composites (Chi-SiO 2 , Chi-CMC-SiO 2 ) were developed. These two types of composites presented a different swelling behavior due to the environmental pH. Moreover, the nanocomposites were loaded with aqueous Larrea divaricata Cav. extract (Ld), a South American plant which presents antioxidant properties suitable for the treatment of gingivoperiodontal diseases. Chi-CMC-SiO 2 composites showed the highest incorporation and reached the 100% of extract release in almost 4 days while they preserved their antioxidant properties. In this study, thermal and swelling behavior were pointed out to show the distinct water-composite interaction and therefore to evaluate their mucoadhesivity. Furthermore, a cytotoxicity test with 3T3 fibroblasts was assessed, showing that in both composites the addition of Larrea divaricata Cav. extract increased fibroblast proliferation. Lastly, preliminary in vitro studies were performed with simulated body fluids. Indeed, SEM-EDS analysis indicated that only chi-SiO 2 composite may provide an environment for possible biomineralization while the addition of CMC to the composites discouraged calcium accumulation. In conclusion, the development of bioactive composites could promote the regeneration of periodontal tissue damaged throughout periodontal disease and the presence of silica nanoparticles could provide an environment for biomineralization. Fil: Alvarez Echazú, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Olivetti, Christian Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Peralta, Ignacio Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Alonso, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Anesini, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Pérez, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Alvarez, Gisela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

The fresh leaves and stems of Ilex paraguariensis (Aquifoliaceae) are employed to prepare the commercial product used in North-eastern Argentina, Southern Brazil and Eastern Paraguay named yerba mate. The presence of polyphenols and xanthines, which present antioxidant activity, has been described in I. paraguariensis. In living organism, reactive oxygen species can cause tissue damage affecting erythrocyte membranes leading to hemolysis. The aim of this work was to evaluate the protective effect of an aqueous extract of I. paraguariensis (green leaves) on the hemolysis of red blood cells induced by hydrogen peroxide and to correlate this activity with the enzymatic activity related to hydrogen peroxide metabolism. The antioxidant activity of chlorogenic acid and caffeine was also analysed to evaluate their contribution to the activity of the crude extract. The extract as well as the isolated compounds protected red blood cells from hemolysis. This effect was related to a catalase-like activity. This study could contribute to the knowledge of the antioxidant activity of I. paraguariensis in view of the great quantities of yerba mate consumed by the population. Copyright © 2012 John Wiley & Sons, Ltd.