Clay minerals have historically played a consequential role in human health. While the beginnings were rooted in geophagy, a primitive act of consuming earth, the health-related uses of clay minerals have evolved and diversified over time. As excipients in pharmaceutical formulations, clay minerals can attribute novel properties onto intercalated compounds. Intercalating oxybenzone, a UV filter, within the interlamellar space of montmorillonite is desirable in order to minimize direct contact with skin. Intercalating resveratrol, a compound known for attributing beneficial effects onto human health, may be advantageous since this compound is susceptible to cis-trans isomerisation. The strategy of using alkylammonium–modified clay was undertaken and proved successful for the intercalation of oxybenzone. The field of biopolymer/layered silicate nanocomposites is heavily researched for use in a multitude of applications. Novel montmorillonite nanocomposites were prepared with neutral guar gum and cationic guar gum, using an environmentally friendly process and are fully characterized.

Duchenne Muscular Dystrophy (DMD) is an x-linked neuromuscular disease that is caused by an absence of dystrophin protein, rendering skeletal muscle more susceptible to contraction-induced damage. One therapeutic strategy focuses on increasing the expression of endogenous utrophin A, a dystrophin homologue. Interestingly, slow muscle is more resistant to the dystrophic pathology and has increased utrophin A expression (Webster 1998; Gramolini 2001b). These observations led researchers to explore the therapeutic potential of stimulating the slow, oxidative myogenic program (SOMP) in the mdx context. Beneficial adaptations were seen with pharmacological activation of PPARδ and AMPK. We treated mdx mice with resveratrol (~100mg/kg/day), a putative SIRT1 activator, for 6-7 weeks and evaluated the activity of phenotypic modifiers that are known to influence the SOMP. SIRT1 activity and protein levels increased significantly, as well as downstream PGC-1α activity. There was evidence of a fibre type conversion as the treated mice had a higher proportion of the slow myosin heavy chain isoforms in both the EDL and Soleus skeletal muscles. Utrophin A protein levels showed modest, but consistent increases with resveratrol treatment. Finally, histological analysis revealed improvements in central nucleation and fibre size variability. These findings were promising, but raised the question of whether modifying the treatment regimen may result in greater therapeutic benefits. Surprisingly, we discovered that an elevated dose of 500mg/kg/day was ineffective in its promotion of the SOMP. SIRT1 was not activated and there was no change in utrophin A levels with resveratrol treatment. Taken together, this study demonstrates that resveratrol has the ability to promote the SOMP through SIRT1 and PGC-1α activation. It also highlights the importance of selecting an appropriate dose of resveratrol to maximize its effectiveness.

Objetivo: Sintetizar la evidencia primaria con respecto a la eficacia y seguridad de los estilbenos en el tratamiento de la sintomatología climatérica en las mujeres de edad mediana. Métodos: Llevamos a cabo una revisión sistemática de la literatura según las recomendaciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Realizamos la búsqueda primaria en Pubmed-Medline, Embase, Scopus, Web of Science, WOS-Medline, LILACS, CINAHL, PsycINFO, SciELO, CENTRAL y en registros internacionales de ensayos clínicos, sobre la eficacia y seguridad de los estilbenos en sintomatología climatérica. Consultamos fuentes de literatura gris, hasta diciembre del 2018, sin restricción de idioma. Usamos la herramienta de la Colaboración Cochrane para la evaluación de riesgo de sesgo de los estudios incluidos. Resultados: Obtuvimos 2752 registros en la búsqueda primaria, a partir de los cuales seleccionamos cuatro ensayos clínicos controlados aleatorizados (ECAs) que reportaron desenlaces de eficacia y seguridad. Existe alta heterogeneidad entre los estudios en cuanto a la dosis, combinaciones con otros fitoestrógenos, duración de la suplementación, escalas de medición y reporte de desenlaces. En cuanto a la eficacia, un estudio reportó disminución significativa en todos los síntomas somáticos, en el grupo con resveratrol, con mayor reducción en el ítem de molestias musculares y articulares, donde solo el 16.7% de la población reportó estas molestias al final de la intervención, comparado a un 73.3% del brazo placebo (p<0.001). Por otro lado, un segundo estudio demostró mejoría significativa en el número (p=0.0077) e intensidad (p=0.018) de los episodios vasomotores en el grupo de la intervención. En contraparte, un tercer estudio mostró diferencias no significativas en el puntaje total de la subescala somática (7.7 ± 2.2; p ITT= 0.760) para el grupo de la intervención y (8.6 ± 2.2; p ITT= 0.760) para el grupo control. En relación a la eficacia de los estilbenos en sintomatología urogenital y psicológica, los resultados fueron contradictorios. En términos de seguridad, dos de los cuatro ECAs reportaron la ausencia de eventos adversos con la suplementación de resveratrol. Conclusión: La evidencia proveniente de los ECAs incluidos no es concluyente con respecto a la eficacia en la suplementación con estilbenos, particularmente con resveratrol, en el manejo de la sintomatología climatérica. Los ensayos clínicos reportaron la ausencia de eventos adversos con la suplementación de resveratrol, aunque este desenlace fue evaluado solo en la mitad de los estudios. Por ello, se requiere llevar a cabo futuros ensayos clínicos aleatorizados con un mejor diseño y mayor muestra, con el fin de alcanzar una conclusión definitiva sobre el uso de estilbenos. / Objective: To synthesize the evidence regarding the efficacy and safety of stilbenes to treat climacteric symptoms in middle-aged women. Methods: We conducted a systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched in Pubmed-Medline, Embase, Scopus, Web of Science, WOS-Medline, LILACS, CINAHL, PsycINFO, SciELO, CENTRAL and international registries of clinical trials, about the efficacy and safety of stilbenes in climacteric symptomatology. We consulted grey literature sources, until December 2018, without language restriction. We used the Cochrane Collaboration tool for risk of bias assessment of the included studies. Results: We obtained 2752 records in the primary search, from which we selected four randomized controlled trials (RCTs) that reported efficacy and safety outcomes. We found that the included clinical trials were highly heterogeneous in terms of dose, combinations with other phytoestrogens, duration of supplementation, measurement scales, and outcome reporting. Regarding efficacy, one trial reported a significant decrease in all somatic symptoms in the resveratrol group, with the most significant reduction in muscular and joint discomfort, where only 16.7% of the population reported these symptoms at the end of the intervention, compared to 73.3% for the placebo arm (p<0.001). On the other hand, a second RCT showed significant improvement in the number (p=0.0077) and intensity (p=0.018) of vasomotor episodes in the intervention group. In contrast, a third trial showed non-significant differences in the somatic subscale total score, (7.7 ± 2.2; p ITT= 0.760) for the intervention group and (8.6 ± 2.2; p ITT= 0.760) for the control group. In terms of safety, two of four RCTs reported the absence of adverse events with resveratrol supplementation. Conclusion: Evidence from included RCTs is inconclusive regarding the efficacy of stilbene supplementation, particularly resveratrol, to manage climacteric symptomatology. Clinical trials reported the absence of adverse events with resveratrol supplementation, although this outcome was assessed in only half of the studies. Thus, future randomized clinical trials with a better design and larger sample are required to reach a definitive conclusion on stilbenes's use. / Tesis

No description available.

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized and could be subjected to further chemical transformations to obtain amino acid derivatives.

Thesis (MSc (Wine Biotechnology))--University of Stellenbosch, 2006. / Resveratrol is a phytoalexin that is produced in the leaves and skins of grape berries in response to biotic and abiotic factors. Substitution and polymerisation of resveratrol units produce an array of compounds which form part of the active disease defence mechanism in grapevine. Wine is one of the major sources of resveratrol in the human diet. Resveratrol is one of the phenolic compounds present in wine that mediates protective effects on human health. It has been shown to prevent the development of cardiovascular disease, cancer and pathogenesis related to inflammation. Red wines contain higher levels of resveratrol than white wines owing to extended maceration times during fermentation on the skins. During white wine vinification skin contact is limited as skins are removed prior to fermentation. Thus, the extraction of resveratrol into white wines is minimal. The principal focus of our research is the development of a wine yeast strain capable of resveratrol production during grape must fermentation. It is proposed that red and white wines produced with such a resveratrol-producing yeast will contain elevated levels of resveratrol, and that added health benefits may be derived from their consumption. Initial work done in our laboratory established that expressing multiple copies of the genes encoding coenzyme A ligase (4CL216) and resveratrol synthase (vst1) in laboratory yeast enabled the yeast to produce resveratrol, conditional to the supplementation of the growth medium with p-coumaric acid. This study focused on the optimisation of resveratrol production in Saccharomyces cerevisiae. It involved the integration and constitutive expression of 4CL216 from hybrid poplar and vst1 from grapevine. Integration and expression of these genes in three laboratory strains was confirmed by Southern and Northern blot analyses. The evaluation of resveratrol production by yeast required the initial optimisation of the analytical techniques. We optimised the method for sample preparation from the intracellular fraction of yeast and devised a procedure for the assay of the extracellular fractions. The LCMSMS method was further developed to encompass detection and quantification of other compounds related to resveratrol production in yeast. Comparison of resveratrol production in three different yeast genetic backgrounds indicated that the onset of production and the resveratrol yield is yeast strain dependent. Precursor feeding studies indicated that p-coumaric acid availability was a factor limiting maximal resveratrol production. Early indications were obtained that endogenously-produced resveratrol may have an impact on yeast viability during extended culture periods. This study has broadened our understanding of the resveratrol production dynamics in S. cerevisiae and provided important indications as to where further optimisation would be beneficial in order to optimally engineer a wine yeast for maximal resveratrol production.

Les inhibiteurs de la protéase virale (IPs) sont utilisés avec succès dans le cadre d'une thérapie anti-VIH-1. L'efficacité de ce traitement est incontestable notamment en terme de réduction de la charge virale et de maintient du taux de lymphocytes CD4 circulants. Depuis l'incorporation des IPs dans la prise en charge thérapeutique, on note une réduction significative de la morbidité et de la mortalité ainsi qu'un allongement de la durée de vie des patients. Cependant, la prise de ces molécules anti-rétrovirales s'accompagne de nombreux effets secondaires. Les plus préoccupants d'entre eux sont : une lipodystrophie partielle, une hyperlipidémie, une insulino-résistance, une athérosclérose prématurée, ainsi que des infarctus du myocarde. Les patients sont également confrontés à l'apparition de maladies généralement associées à l'âge telles que la neurodégenérescence, l'ostéopénie et le développement de tumeurs malignes. Les mécanismes cellulaires et moléculaires impliqués dans ces altérations métaboliques n'ont pas encore été élucidés. L'objectif de cette étude était d'étudier les effets cellulaires de quatre IPs (Atazanavir, Lopinavir, Ritonavir et Saquinavir) sur la cellule musculaire striée squelettique humaine. Ces travaux ont permis d'identifier une augmentation de la production d'espèces oxygénées réactives (ERO), une altération morphologique du réticulum sarco/endoplasmique (RS/RE) ainsi qu'une augmentation de l'expression de CHOP, un marqueur du stress de ce compartiment et une diminution de l'expression et de la localisation dans les microdomaines membranaires (lipid rafts) de la cavéoline 3 et de la flotilline 1. Enfin, l'utilisation d'un antioxydant, le Resvératrol protége le myotube primaire humain de ces différentes altérations engendrées par les IPs. Ces données suggèrent un rôle central de la surproduction d'ERO dans le développement du stress du RE/RS et de la perte de localisation des protéines résidantes des microdomaines membranaires. De plus , en l'absence de persceptive vaccinale concrète, le Resvératrol, au travers de ces effets protecteurs, pourrait se révéler un atout de choix dans l'atténuation des effets secondaires des IPs en contribuant ainsi à l'amélioration de la prise en charge du patient séropositif. / HIV protease inhibitors (PI) have been successfully used in highly active antiretroviral therapy (HAART) of HIV-1 infection, the most effective treatment currently available. Incorporation of protease inhibitors in HAART has significantly reduced the morbidity and mortality and prolonged the lifespan of patients with HIV infection. Protease inhibitor benefits are unfortunately compromised by a number of clinically important adverse side-effects. Most patients on HAART develop a metabolic syndrome associated with partial lipodystrophy, hyperlipidemia, insulin resistance, premature atherosclerosis and myocardial infarction. Moreover, these patients face a growing number of other age-related comorbidities, such as neurodegeneration, osteopenia and malignancies. The cellular and molecular mechanisms underlying protease inhibitor-associated metabolic abnormalities remain elusive, but they seem to be related to overproduction of reactive oxygen speci es (ROS), induction of endoplasmic reticulum stress and activation of the unfolded protein response (UPR). The objective of this thesis was to determine the cell effects of four PIs (Atazanavir, Lopinavir, Ritonavir and Saquinavir) in cultures of primary human skeletal myotubes. This study showed that PIs increased ROS production, altered sarco/endoplasmic reticulum (SR/ER) morphology, increased expression of C/EBP homologous protein, a SR/ER stress marker, and decreased expression and localization at lipid rafts of Caveolin 3 and Flotillin 1. In addition, we showed that the antioxidant Resveratrol protected the human primary myotube of these iatrogenic effects. These data suggest a central role of the overproduction of ERO in the development of SR/ER stress and mislocalization of lipid raft proteins induced by PIs. Besides, in absence of vaccine, Resveratrol may be used by a potentiel therapeutic agent to attenuate PI-induced side effects

L’arthrose est une maladie dégénérative de l’articulation caractérisée par une dégradation du cartilage, une inflammation de la membrane synoviale et un remodelage de l’os sous-chondral. En conditions physiologiques, les chondrocytes, seul type cellulaire du cartilage, sont en hypoxie (≈ 2% d’oxygène). Le cartilage étant un tissu avascularisé, il existe un gradient de concentration en oxygène au sein des différentes couches du cartilage. Lors du développement de l’arthrose, la dégradation du cartilage provoque une rupture de ce gradient, exposant ainsi les cellules des couches profondes à des concentrations en oxygène beaucoup plus élevées et induisant des modifications de leur métabolisme, ce qui induit leur dysfonction. Le syndrome métabolique est défini par un ensemble de perturbations glucidiques, lipidiques et vasculaires menant au développement de maladies cardiovasculaires et au diabète de type 2. Récemment, un lien entre arthrose et syndrome métabolique a été suggéré, introduisant une notion d’arthrose métabolique. Au cours de cette étude, nous nous sommes intéressés au lien entre arthrose, syndrome métabolique et stress oxydant induit par de fortes concentrations de glucose. Dans la première partie de ce travail, nous avons étudié les effets in vitro de 25 mM de glucose sur une lignée de chondrocytes humains immortalisés (T/C28a2), en hypoxie (2% d’oxygène) et en normoxie (21% d’oxygène). Nous avons montré que le glucose à 25 mM induisait la production d’espèces réactives de l’oxygène (ERO) et de l’azote, l’activation de la caspase 3, la production d’interleukine 6 (IL-6), la diminution de l’activité lysyl oxydase (LOX), qui est impliquée dans les liaisons de pontage des fibres de collagène et d’élastine, ainsi que l’activation du système thiorédoxine (Trx). Ce dernier est un système de défense anti-oxydant endogène composé de la thiorédoxine, de la thiorédoxine réductase (TR) et de Txnip, qui intervient dans le maintien de l’homéostasie cellulaire en réduisant les protéines oxydées, contrôlant ainsi l’environnement redox des cellules. Les effets du glucose 25 mM ont été observés dans les deux conditions d’oxygène étudiées, cependant la réponse cellulaire en normoxie était plus précoce qu’en hypoxie. Nous avons également pu mettre en évidence un rôle de régulateur négatif de la Trx-1 sur la production d’IL-6 faisant intervenir la voie de signalisation p38MAPK. Dans la deuxième partie de ce travail, nous nous sommes intéressés aux effets de l’apport exogène de resvératrol sur les modifications induites par le glucose à 25 mM. Le resvératrol (3,4’,5-trihydroxystilbène) est un polyphénol de la famille des stilbènes, connu pour ses multiples propriétés anti-oxydantes, anti-inflammatoires, anti-diabétiques et anti-cancer. Nous avons pu observer que le resvératrol à 25 μM était capable de diminuer les effets délétères provoqués par le glucose à 25 mM. Cependant, la biodisponibilité du resvératrol est très limitée, empêchant son utilisation en thérapeutique humaine. Par conséquent, dans la troisième partie de cette étude, nous nous sommes intéressés au développement de nouvelles formulations galéniques de resvératrol (nano-émulsions (NE)) et à leurs effets sur un modèle de cellules endothéliales aortiques bovines (BAEC), sur les T/C28a2 ainsi que sur des chondrocytes humains en culture primaire provenant de cartilage de patients arthrosiques. Nous avons montré qu’une des NE permettait d’augmenter le passage intracellulaire de resvératrol dans les deux modèles étudiés et d’en potentialiser les effets protecteurs contre un stress oxydant. Cette NE s’est également montrée efficace dans le rétablissement de l’activité LOX dans les cellules de patients arthrosiques. En conclusion, nous avons montré que le glucose à 25 mM avait des effets délétères sur les chondrocytes de la lignée T/C28a2 et que l’apport exogène de resvératrol permettait de lutter contre ses effets. (...) / Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation of synovial membrane and subchondral bone remodelling. Under physiological conditions, chondrocytes - the only cell type found in cartilage - are under hypoxia (around 2% of oxygen). As cartilage is an avascular tissue, an oxygen gradient is established from the superficial to the deeper layers. During OA development, cartilage degradation is responsible for a break in this gradient; consequently, cells from the deepest layers are exposed to higher oxygen concentrations inducing modifications in cell metabolism leading to their dysfunction. Metabolic syndrome (MetS) is defined by a cluster of factors (impairment of glucose and lipid metabolism, vascular dysfunctions…) leading to cardiovascular diseases and type 2 diabetes development. Recently, a link between OA and MetS has been suggested, introducing a notion of metabolic OA. We have focused our study on the link between OA, MetS and oxidative stress induced by high glucose concentrations. In the first part of this study, we have determined the in vitro effects of 25 mM glucose on an immortalized human chondrocyte cell line (T/C28a2), under hypoxia (2% oxygen) and normoxia (21% oxygen). We demonstrated that 25 mM glucose induced radical oxygen species (ROS) and nitric oxide production, caspase 3 activation, interleukin 6 (IL-6) production, decrease in lysyl oxidase (LOX) activity (involved in type II collagen crosslinks), and activation of the thioredoxin (Trx) system. Trx system is an endogenous anti-oxidant system, composed by thioredoxin, thioredoxin reductase (TR) and Txnip; it is involved in cellular homeostasis by reducing oxidized proteins, thereby controlling cellular redox environment. Effects of 25 mM glucose have been observed under both oxygen conditions; nevertheless, cellular response under normoxia underwent earlier than under hypoxia. We have also highlighted Trx-1 as a negative regulator of IL-6 production through p38MAPK signalling pathway. In the second part of this study, we have focused our work on the effects of the addition of an exogenous antioxidant, i.e. resveratrol, on the modifications induced by 25 mM glucose. Indeed, resveratrol (3,4’,5-trihydroxystilbene) is a polyphenol of the stilbene family, known for its multiple anti-inflammatory, anti-oxidative, anti-diabetes and anti-cancer properties. We have observed that 25 μM resveratrol was able to decrease deleterious effects induced by 25 mM glucose. However, resveratrol bioavailability is very low, avoiding its use in human therapeutic strategy. Consequently, in the third part of this study, we have developed new galenic formulations of resveratrol, i.e. nano-emulsions (NEs) and determined their effects on a bovine aortic endothelial cells (BAEC) model, on T/C28a2 cells and also on primary cultures of human chondrocytes from osteoarthritic cartilages. One of our NEs was able to increase resveratrol intracellular passage in both cellular models, and to increase the protective effects of resveratrol against oxidative stress. This NE was also efficient in the normalization of LOX activity in osteoarthritic chondrocytes. To conclude, we have demonstrated that 25 mM glucose induced deleterious effects on chondrocytes of the T/C28a2 cell line, and that an exogenous supply in resveratrol allowed to counteract these effects. Development of a new galenic formulation of resveratrol opens new interesting prospects in human therapeutic strategy against OA associated with MetS.

Transtorno do espectro do autismo (TEA) é um transtorno do neurodesenvolvimento caracterizado por perturbações na comunicação social e pela manifestação de comportamentos, interesses e atividades repetitivos e restritos. Embora a etiologia do autismo ainda seja desconhecida, fortes evidências mostram que a causa pode residir em uma complexa interação de fatores genéticos e ambientais durante o desenvolvimento. A exposição pré-natal ao ácido valproico (VPA) é um dos fatores de risco ambiental mais bem estabelecidos. Por isso, o VPA é comumente utilizado para desencadear um fenótipo do tipo autista em animais. Estudos prévios do nosso grupo demonstram que o tratamento com resveratrol (RSV) aplicado a ratas prenhes foi capaz de prevenir os prejuízos no comportamento social induzidos na prole do grupo VPA. As vias de sinalização CK2/PTEN e AKT/GSK-3β estão relacionadas a processos de plasticidade celular e conectividade neuronal, que são processos que exercem grande impacto em diversos parâmetros, incluindo o comportamento social. Assim, os objetivos deste trabalho foram: 1) avaliar o impacto da exposição pré-natal ao VPA sobre as vias CK2/PTEN e AKT/GSK-3β, nas regiões da amígdala e do hipocampo de ratos machos adultos de 120 dias e 2) avaliar o possível efeito protetor da exposição intra-útero ao RSV sobre as alterações causadas pelo VPA nas vias CK2/PTEN e AKT/GSK-3β. O tratamento com RSV combinado com o VPA induziu uma inibição da PTEN e GSK-3β na amígdala, e o RSV teve um efeito per se, inibindo a GSK-3β nesta mesma estrutura. Além disso, O VPA induziu um aumento de atividade da AKT e redução dos níveis proteicos totais de AKT e PTEN no hipocampo. O RSV foi capaz de prevenir estas alterações, com exceção aos níveis proteicos de AKT. Portanto, nossos resultados indicam que a exposição pré-natal ao VPA altera vias de sinalização importantes durante o desenvolvimento neural, e o tratamento com RSV foi capaz de prevenir alguns de seus efeitos. Estes resultados são muito promissores para estudos futuros e contribuem para uma maior compreensão sobre os processos relacionados com a indução de comportamentos do tipo autista pelo VPA e o possível mecanismo de prevenção do RSV sobre o comportamento social. / Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disabilities in social communication and repetitive and stereotyped behaviour, interests and activities. Although the etiology is still unknown, there is growing evidence suggesting that the cause lies on a complex interaction between genetic and environmental factors during the development. The pre-natal exposure to valproic acid (VPA) is one of the most well established environmental risk factors. Therefore, the VPA is commonly used to induce an autistic-like phenotype in animals. Previous studies from our group shows that the treatment of pregnant rats with resveratrol (RSV) prevented the social behavior deficits induced in the male offspring of the VPA group. The CK2/PTEN and AKT/GSK-3β pathways are related to processes of cellular plasticity and neuronal connectivity, which are processes that exert a huge impact in several parameters, including the social behavior. Thus, the objectives of this work were: 1) to evaluate the impact of the pre-natal exposure to VPA in the CK2/PTEN and AKT/GSK-3β pathways, in amygdala and hippocampus of adult male rats with 120 days old and 2) to evaluate the possible protective effect of the intra-womb exposition to RSV on VPA-induced changes in CK2/PTEN and AKT/GSK-3β pathways. The treatment with RSV combined with VPA induced an inhibition of PTEN and GSK-3β in amygdala, and the RSV had an effect per se, inhibiting GSK-3β in the same structure. Furthermore, the VPA induced an increase in activity of AKT and a reduction in total protein levels of AKT and PTEN in hippocampus. The RSV prevented these effects, with exception of the protein levels of AKT. Thus, our results indicate that the pre-natal exposition to VPA changes important signaling pathways during the neural development, and the treatment with RSV prevented some of its effects. These findings are very promising for future studies and contribute for a better understanding about processes related to the induction of autistic-like behaviors by VPA and the possible mechanism of prevention by RSV on the social behavior.

<p>This investigation focused on Rhoicissus tomentosa, belonging to the family, Vitaceae in an attempt to assess the phytochemistry of this plant which is widely used by traditional healers in South Africa to ensure the safe delivery during pregnancy and childbirth (Hutchings et al., 1996).</p>