Interferons are key cytokines acting on pancreatic islets in type 1 diabetes.

AIMS/HYPOTHESIS: The proinflammatory cytokines IFN-α, IFN-γ, IL-1ß and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown. METHODS: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes. RESULTS: IFN-α and IFN-γ had a greater impact on the beta cell transcriptome when compared with IL-1ß and TNF-α. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from individuals with type 1 diabetes, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to 'danger signals' such as viral infections. Zinc finger NFX1-type containing 1 (ZNFX1), a double-stranded RNA sensor, was identified as highly induced by IFNs and shown to play a key role in the antiviral response in beta cells. CONCLUSIONS/INTERPRETATION: These data suggest that IFN-α and IFN-γ are key cytokines at the islet level in human type 1 diabetes, contributing to the triggering and amplification of autoimmunity.

Zein nanoparticles as oral carrier for mometasone furoate delivery.

Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to its poor bioavailability we further investigated whether nanoparticles (NPs) made of zein protein may constitute a safe and effective choice to incorporate MF. Thus, in this work, we loaded MF into zein NPs aiming to evaluate possible advantages that could result from oral delivery and extend the range of MF application such as inflammatory gut diseases. MF-loaded zein NPs presented an average size in the range of 100 and 135 nm, narrow size distribution (polydispersity index < 0.300), zeta potential of around + 10 mV and association efficiency of MF over 70%. Transmission electron microscopy imaging revealed that NPs had a round shape and presented a smooth surface. The zein NPs showed low MF release in a buffer that mimics the gastric condition (pH = 1.2) and slower and controlled MF release in the intestinal condition (pH = 6.8). The short and intermediate safety of zein NPs was confirmed assessing the incubation against Caco-2 and HT29-MTX intestinal cells up to 24 h. Permeability studies of MF across Caco-2/HT29-MTX co-culture monolayer evidenced that zein NPs modulated MF transport across cell monolayer resulting in a stronger and prolonged interaction with mucus, potentially extending the time of absorption and overall local and systemic bioavailability. Overall, zein NPs showed to be suitable to carry MF to the intestine and future studies can be developed to investigate the use of MF-loaded zein NPs to treat intestinal inflammatory diseases.

Coadministration of olanzapine causes minor impacts on the diabetogenic outcomes induced by dexamethasone treatment in rats.

AIMS: Investigate whether the coadministration of olanzapine exacerbates the diabetogenic effects of dexamethasone, two agents used in the antiemetic cocktails indicated to mitigate the adverse effects of chemotherapy. MAIN METHODS: Adult Wistar rats (both sexes) were treated daily with dexamethasone (1 mg/kg, body mass (b.m.), intraperitoneal (i.p.)) with or without olanzapine (10 mg/kg, b.m., orogastric (o.g.)) for 5 consecutive days. During and at the end of the treatment, we evaluated biometric data and parameters involving glucose and lipid metabolism. KEY FINDINGS: Dexamethasone treatment resulted in glucose and lipid intolerance, higher plasma insulin and triacylglycerol levels, higher content of hepatic glycogen and fat, and higher islet mass in both sexes. These changes were not exacerbated by concomitant treatment with olanzapine. However, coadministration of olanzapine worsened the weight loss and plasma total cholesterol in males, while in females resulted in lethargy, higher plasma total cholesterol, and higher hepatic triacylglycerol release. SIGNIFICANCE: Coadministration of olanzapine does not exacerbate any diabetogenic dexamethasone effect on glucose metabolism and exerts a minor impact on the lipid homeostasis of rats. Our data favor the addition of olanzapine in the antiemetic cocktail considering the low incidence of metabolic adverse effects for the period and dosage analyzed in male and female rats.

Oral mometasone furoate administration preserves anti-inflammatory action with fewer metabolic adverse effects in rats.

BACKGROUND: Exogenous glucocorticoids (CGs) possess relevant therapeutic effects but exert diabetogenic actions when in excess. Thus, ligands with potential therapeutic applications and fewer adverse effects are needed. To this, we analyzed whether mometasone furoate (MF), a CG expected to cause fewer side effects, given through systemic routes, could maintain the anti-inflammatory actions without relevant repercussions on metabolism. METHODS: The anti-inflammatory effect of MF was evaluated with both peritonitis and colitis models in rodents. Glucose and lipid metabolism were investigated in male and female rats treated daily with MF with different doses and routes of administration for seven days. The involvement of glucocorticoid receptor (GR) on MF actions was assessed in animals pretreated with mifepristone. Also, the potential reversibility of the adverse effects was assessed. Dexamethasone was used as a positive control. RESULTS: MF treatment resulted in glucose intolerance in male rats treated through intraperitoneal (ip) but not oral gavage route (og). In female rats, none of the routes led to glucose intolerance. MF treatment attenuated insulin sensitivity and increased pancreatic ß-cell mass, regardless of the sex and route of administration. MF treatment through og route did not result in dyslipidemia, as observed in rats treated through the ip route (both sexes). The anti-inflammatory and metabolic adverse effects of MF were GR-dependent, and metabolic outcomes altered by MF administration were reversible. CONCLUSION: MF maintains anti-inflammatory activity when administered by systemic routes and exerts less impact on metabolism when administered orally in male and female rats, effects that are GR-dependent and reversible. Category: Metabolic Disorders and Endocrinology.

Preconception exposure to malathion and glucose homeostasis in rats: Effects on dams during pregnancy and post-term periods, and on their progeny.

Understanding the individual and global impact of pesticides on human physiology and the different stages of life is still a challenge in environmental health. We analyzed here whether administration of the organophosphate insecticide malathion before pregnancy could affect glucose homeostasis during pregnancy and, in addition, generate possible later consequences in mothers and offspring. For this, adult Wistar rats were allocated into two groups and were treated daily (intragastric) with malathion (14 or 140 mg/kg, body mass (bm)) for 21-25 days. Corn oil was used as vehicle in the Control group. Subgroups were defined based on the absence (nulliparous) or presence (pregnant) of a copulatory plug. Pregnant rats were followed by an additional period of 2 months after the term (post-term), without continuing malathion treatment. Fetuses and adult offspring of males and females were also evaluated. We ran an additional experimental design with rats exposed to malathion before pregnancy at a dose of 0.1 mg/kg bm. Malathion exposure resulted in glucose intolerance in the mothers during pregnancy and post-term period, regardless of the exposure dose. This was accompanied by increased visceral adipose tissue mass, dyslipidemia, unchanged pancreatic ß-cell mass, and varying insulin responses to glucose in vivo. The number of total newborns and birthweight was not affected by malathion exposure. Adult offspring from both sexes also became glucose-intolerant, regardless of the pesticide dose their dams were exposed to. This alteration could be associated with changes at the epigenomic level, as reduced hepatic mRNA content of DNA methylases and demethylases was found. We demonstrated that periconceptional exposure to malathion with doses aiming to mimic from work environment to indirect contamination predisposes progenitors and offspring rats to glucose intolerance. Thus, we conclude that subchronic exposure to malathion is a risk factor for gestational diabetes and prediabetes later in life.

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Abstract Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid.

Myrsinoic acid B from Myrsine coriacea reverses depressive-like behavior and brain oxidative stress in streptozotocin-diabetic rats.

AIMS: Major depressive disorder (MDD) affects approximately 322 million people worldwide and is a common comorbidity in patients with diabetes mellitus (DM). A possible pathophysiological mechanism correlating both diseases is the increased oxidative stress in brain regions due to hyperglycemia. Myrsine coriacea (Primulaceae) is popularly known as "capororoca" and studies have been shown that this plant exhibits several pharmacological properties attributed to myrsinoic acid A (MAA) and B (MAB). Indeed, previous results have been shown its effects on the central nervous system, leading us to explore possible psychotropic effects. MAIN METHODS: The effects of treatment with hydroalcoholic extract of the barks from Myrsine coriacea (HEBMC, 150 mg/kg, o.g.), MAA (5 mg/kg, o.g.), and MAB (3 mg/kg, o.g.) were evaluated in streptozotocin (75 mg/kg, i.p.)-induced diabetic female rats. After 28 days of treatments, rats were submitted to the forced swim test (FST) and open field test (OFT). Also, superoxide dismutase (SOD) and catalase (CAT) activities, reduced glutathione (GSH) and lipid hydroperoxides (LOOH) levels were evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of these rats. KEY FINDINGS: The treatment with MAA or MAB increased the latency of first immobility in diabetic rats, and the HEBMC administration decreased the immobility time, and increase the climbing in FST. However, only MAB treatment reduces the immobility time, increases the climbing, and swimming in FST, and increases the crossing of diabetic animals in the OFT. Besides, this behavioral improvement promoted by MAB administration was accompanied by reducing in oxidative stress in the HIP and PFC, but not reducing hyperglycemia in diabetic rats. SIGNIFICANCE: The results suggest that MAB's antioxidant effect in the HIP of diabetic animals may be essential to its antidepressant-like effect.

Reduced insulin sensitivity and increased ß/α cell mass is associated with reduced hepatic insulin-degrading enzyme activity in pregnant rats.

AIMS: Pregnancy is associated with the development of a transitory insulin resistance that parallels with the upregulation of pancreatic ß-cell function and mass. These metabolic adaptations guarantee the higher insulin demand, but there is no evidence of whether insulin clearance contributes to this process. Thus, we investigated some of the hepatic parameters related to insulin clearance during rat pregnancy. We also investigated some molecular parameters in the hypothalamus. MAIN METHODS: We evaluated the body mass and food intake, insulin sensitivity, ß- and α-cell masses, insulin clearance based on an exogenous insulin load, hepatic insulin-degrading enzyme (IDE) activity, and hepatic and hypothalamic protein content of IDE and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) in three periods of gestation in Wistar rats. KEY FINDINGS: In the first week of pregnancy, both insulin sensitivity and clearance increased, a pattern that inverted in the third week of gestation (reduced insulin sensitivity and clearance). Diminished insulin clearance was associated with lower hepatic IDE activity and higher pancreatic ß- and α-cell masses. No alteration in the hepatic IDE and CEACAM protein content was observed throughout pregnancy, but hypothalamic IDE protein content was significantly reduced in the late gestation period. SIGNIFICANCE: In conclusion, elevated insulin demand in the late period of gestation occurs not only as a result of increased ß-cell mass and function but also by a potential reduction in hepatic insulin clearance. Knowing this physiological process may be valuable when considering gestational diabetes mellitus results from a failure in insulin supply during pregnancy.

Plumieride exerts anxiolytic-like effect mediated by GABAergic and monoaminergic systems.

Plumieride (PLU), an iridoid isolated from Allamanda cathartica flowers, has been studied by our research group due to its anti-inflammatory potential, antidepressant-like and anxiolytic-like effects. This research investigated the involvement of GABAergic and monoaminergic systems in the anxiolytic-like effect elicited by PLU. Therefore, mice were pre-treated with GABAergic, serotonergic, adrenergic or dopaminergic receptor antagonists (i.p.), and exposed to Elevated Plus-Maze (EPM) and Open-Field Test (OFT). The preliminary results revealed that PLU (p.o.) possibly interacts with the mentioned systems through the GABAA, GABAB, 5-HT1A, 5-HT3, α1, α2, and D2 receptors.

Antidepressant-like effect of hydroalcoholic extract from barks of Rapanea ferruginea: Role of monoaminergic system and effect of its isolated compounds myrsinoic acid A and B.

Major Depressive Disorder (MDD) is a highly disabling condition and has been linked to increased inflammatory mediators. Hydroalcoholic extract from barks of Rapanea ferruginea (HEBRF) and the majoritary compounds-myrsinoic acid A (MAA) and B (MAB)-have been studied due to their anti-inflammatory potential, but there is no evidence about its antidepressant-like effects. This research investigated the HEBRF, MAA, and MAB antidepressant-like effect, besides the involvement of the monoaminergic system and MAO-A activity in the HEBRF antidepressant-like effect. HEBRF (50-300 mg/kg, p.o.), MAA (5-30 mg/kg, p.o.) or MAB (3-60 mg/kg, p.o.) were administrated to mice, and behavioral parameters were assessed using the tail suspension test (TST), splash test (ST) and open field test (OFT). The involvement of monoaminergic system in the HEBRF antidepressant-like effect was established through the pretreatment of mice with antagonists. The influence triggered by HEBRF in the monoamine oxidase A (MAO-A) activity was evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of mice. HEBRF (100-300 mg/kg) promoted antidepressant-like effect in the TST and augmented the total time of grooming in the ST, without compromising the locomotor activity. Pretreatment of mice with serotoninergic, dopaminergic, and noradrenergic antagonists, reversed the HEBRF antidepressant-like effect. Besides, HEBRF inhibited the MAO-A activity in the HIP and PFC. Moreover, MAA (5 mg/kg) and MAB (3 mg/kg) also promoted antidepressant-like and anti-anhedonic effects in mice. Data showed that monoaminergic system is involved in the HEBRF antidepressant-like effect, besides MAA and MAB possibly could be responsible for these pharmacological effects.

Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer's disease: Effects against scopolamine and streptozotocin-induced cognitive dysfunctions.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death, characteristic of the effect of time on biochemical neuronal function. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research, since the standard drugs have many side effects. Taraxerol (TRX) is a triterpene that has been isolated from several plant species, and its various pharmacological properties have already been identified, such the acetylcholinesterase (AChE) inhibition activity in vitro. There is a lack of information in literature that confirms the effect of TRX in an animal AD-like model. Seeking to fill this gap in the literature, in the present work we assessed the effect of TRX on AChE activity in the animals' encephalon and hippocampus. We also investigated the effect of TRX (1.77 µM/side, 0.5 µL) isolated from leaves of Eugenia umbelliflora Berg. on aversive memory impairments induced by scopolamine (2 µg/side, 0.5 µL) infused into rat hippocampus, and the effect of TRX (0.89 and 1.77 µM/side, 0.5 µL) on aversive memory impairments induced by streptozotocin (STZ) (2.5 mg/mL, 2.0 µL) infused i.c.v. into mice, using the step-down inhibitory avoidance task. We found that TRX significantly inhibited AChE activity in the animal's hippocampus. Furthermore, TRX significantly improved scopolamine and STZ-induced memory impairment. Taking together, these results confirms its AChE activity inhibition in animals and indicate that TRX has anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in AD.

Avaliação psicofarmacológica do óleo essencial de Piper amplum / Psychopharmacology analysis of essential oil Piper amplum

Espécies do gênero Piper são utilizadas na medicina popular e carecem de validação farmacológica. Estudos científicos com a espécie Piper amplum são concentrados principalmente nos efeitos antimicrobianos e pouco se sabe sobre suas ações sobre o sistema nervoso central (SNC), apesar da planta ser utilizada de forma etnofarmacológica em processos neurológicos. Portanto, para avaliar os efeitos sobre o SNC, o óleo essencial obtido de Piper amplum (OEPA) (50, 100, 150 mg/kg, v.o.) foi administrado em camundongos fêmeas Swiss (25-30 g/ n=8-10 animais) e 60 minutos após os mesmos foram submetidos a testes de: depressão (teste do nado forçado, TNF), deambulação motora (campo aberto, TCA e Rotarod), convulsão e hipnose. Grupos controle-positivo (fármacos usados na terapêutica) e negativo (veículo no qual o OEPA foi dissolvido) foram utilizados nas mesmas condições experimentais. Os resultados demonstraram que o tratamento com OEPA não afetou a deambulação e atividade exploratória dos animais no TCA, assim como não afetou o sistema motor no Rotarod. Não foram detectados efeitos anticonvulsivante, hipnótico e ansiolítico do OEPA, entretanto, verificou-se atividade antidepressiva no TNF nas doses testadas. Diante dos efeitos do OEPA sobre o SNC, pode-se considerar o mesmo como alvo potencial para maiores estudos relacionados a atividade antidepressiva.(AU)

Species of the genus Piper used are in folk medicine and need pharmacological validation. Scientific studies with Piper amplum species are mainly concentrated on antimicrobial effects, little known is about their actions on the central nervous system (CNS), although the plant is ethnopharmacological used in neurological processes. Therefore, to evaluate the effects on the CNS, the essential oil obtained from Piper amplum (OEPA) (50, 100-150 mg/kg, p.o.) was administered in Swiss female mice (25-30 g/ n=8-10 animals) and 60 minutes after, the same were submitted to tests: depression forced swimming test, FST), motor ambulation (open field, OFT and Rotarod), seizure and hypnosis. Control-positive (drugs used in therapy) and negative (vehicle in which OEPA was dissolved) control groups were used under the same experimental conditions. The results showed that OEPA treatment did not affect the ambulation and exploratory activity of the animals in the OFT, and did not it affect the motor system in Rotarod. No anticonvulsive, hypnotic and anxiolytic effects of OEPA detected were, however, antidepressant activity in TNF at all doses tested. In view of the effects demonstrated by the OEPA on the CNS, it be can considered the same as a potential target for further studies related to antidepressant activity.(AU)

Antimycoplasmic activity and seasonal variation of essential oil of Eugenia hiemalis Cambess. (Myrtaceae).

The purpose of this work was to study the chemical composition and antimycoplasmic and anticholinesterase activities of the essential oil of Eugenia hiemalis leaves collected throughout the year. A total of 42 compounds were identified by CG, and are present in almost every seasons. Sesquiterpenes were dominant (86.01-91.48%), and non-functionalised sesquiterpenes comprised the major fraction, which increased in the summer; monoterpenes were not identified. The major components were spathulenol (5.36-16.06%), δ-cadinene (7.50-15.93%), bicyclogermacrene (5.70-14.24%) and ß-caryophyllene (4.80-9.43%). The highest oil yield was obtained in summer and autumn. Essential oils presented activity against three evaluated Mycoplasma strains, but no activity was observed in the anticholinesterase assay.

Antimicrobial (including antimollicutes), antioxidant and anticholinesterase activities of Brazilian and Spanish marine organisms – evaluation of extracts and pure compounds

Abstract This work describes the antimicrobial, antioxidant and anticholinesterase activities in vitro of organic extracts from fourteen seaweeds, eleven sponges, two ascidians, one bryozoan, and one sea anemone species collected along the Brazilian and Spanish coast, as well as the isolation of the diterpene (4R, 9S, 14S)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) and halogenated sesquiterpene elatol (2). The most promising antimicrobial results for cell wall bacteria were obtained by extracts from seaweeds Laurencia dendroidea and Sargassum vulgare var. nanun (MIC 250 μg/ml), and by the bryozoan Bugula neritina (MIC 62.5 μg/ml), both against Staphylococcus aureus. As for antimollicutes, extracts from seaweeds showed results better than the extracts from invertebrates. Almost all seaweeds assayed (92%) exhibited some antimicrobial activity against mollicutes strains (Mycoplasma hominis,Mycoplasma genitalium,Mycoplasma capricolum and Mycoplasma pneumoniae strain FH). From these seaweeds, A1 (Canistrocarpus cervicornis), A11 (Gracilaria sp.) and A4 (Lobophora variegata) showed the best results for M. pneumoniae strain FH (MIC 250 μg/ml). Furthermore, compounds 1 and 2 were also assayed against mollicutes strains M. hominis,M. genitalium,M. capricolum,M. pneumoniae strain 129 and M. pneumoniae strain FH, which showed MIC > 100 μg/ml. Antioxidant activities of extracts from these marine organisms were inactive, except for E7 (from sponge Ircinia sp.), which exhibited moderated antioxidant activities for two methods assayed (IC50 83.0 ± 0.1 μg/ml, and 52.0 ± 0.8 mg AA/g, respectively). Finally, for the anticholinesterase activity, all the 29 samples evaluated (100%) exhibited some level of activity, with IC50 < 1000 μg/ml. From these, seaweeds extracts were considered more promising than marine invertebrate extracts [A10 (IC50 14.4 ± 0.1 μg/ml), A16 (IC50 16.4 ± 0.4 μg/ml) and A8 (IC50 14.9 ± 0.5 μg/ml)]. The findings of this work are useful for further research aiming at isolation and characterization of active compounds.

Efeitos da fração acetato de etila de Tabernaemontana catharinensis sobre respostas glicêmicas e estresse oxidativo de Rattus norvegicus diabéticos / Effects of tabernaemontana catharinensis ethyl acetate fraction on glycemic responses and oxidative stress

OBJECTIVE: To evaluate the Tabernaemontana catharinensis ethyl acetate fraction hypoglycemic and antioxidant activity through the peripheral glycemic dosage and enzymatic tests. Methods: Male rats were divided into 6 groups: control, diabetic control, control extract 50, diabetic extract 50, control extract 80, diabetic extract 80. In diabetic group animals alloxan (150mg/Kg) was administered to induce Diabetes Mellitus. The animals were beheaded following 15 days of treatment with extract or distilled water and the blood was collected in order to perform oxidative stress tests. Results: The diabetic control group showed high levels of glucose, increased levels of thiobarbituric acid and superoxide dismutase activity, and decreased activity of catalase and glutathione peroxidase enzymes. The diabetic animals that received 50mg/Kg and 80mg/Kg of extract showed a decrease in thiobarbituric acid levels and an increase of glutathione peroxidase activity when compared to the diabetic control group. It was observed that only animals treated with 80mg/Kg of extract had positive results regarding superoxide dismutase. Conclusions: The Tabernaemontana catharinensis ethyl acetate fraction when orally administered for 14 consecutive days at doses of 50mg/Kg and 80mg/Kg reduces the oxidative stress induced by alloxan administration

OBJETIVO: Avaliar a ação hipoglicemiante e antioxidante da fração acetato de etila do extrato de Tabernaemontana catharinensis através da dosagem glicêmica periférica e testes enzimáticos. MÉTODOS: Ratos machos foram divididos em seis grupos: controle, controle diabético, controle extrato 50, diabético extrato 50, controle extrato 80, diabético extrato 80. Nos animais dos grupos diabéticos foi induzida Diabetes Mellitus pela administração de 150mg/Kg de aloxana. Após 15 dias de tratamento com a fração acetato de etila de Tabernaemontana catharinensis ou água destilada, os animais foram decapitados e o sangue foi coletado para realização dos testes de estresse oxidativo. RESULTADOS: O grupo controle diabético apresentou níveis elevados de glicose, aumento dos níveis de ácido tiobarbitúrico e atividade da superóxido dismutase, e diminuição da atividade das enzimas catalase e glutationa peroxidase. Os animais dos grupos diabéticos tratados com 50 e 80mg/Kg do extrato apresentaram redução nos níveis de ácido tiobarbitúrico e aumento da atividade de glutationa peroxidase quando comparado ao grupo controle diabético. Apenas os animais que receberam o extrato na dose de 80mg/Kg obtiveram resultados positivos em relação ao superóxido dismutase. CONCLUSÕES: A fração acetato de etila de Tabernaemontana catharinensis, quando administrada por 14 dias consecutivos, via oral, nas doses de 50 e 80mg/Kg, promove redução nos níveis de estresse oxidativo gerado pela administração de aloxana