Dexamethasone-Induced Insulin Resistance Attenuation by Oral Sulfur-Oxidovanadium(IV) Complex Treatment in Mice.

Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound-[VIVO(octd)]-and effects associated with glucocorticoid-induced insulin resistance in mice. The effects of [VIVO(octd)] were evaluated in a female Swiss mice model of insulin resistance induced by seven days of dexamethasone treatment in comparison with groups receiving metformin treatment. Biological assays such as hematological, TyG index, hepatic lipids, glycogen, oxidative stress in the liver, and oral glucose tolerance tests were evaluated. [VIVO(octd)] was characterized with 51V NMR, infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR), electronic absorption spectroscopy, and mass spectrometry (ESI-FT-MS). The [VIVO(octd)] oral treatment (50 mg/kg) had an antioxidant effect, reducing 50% of fast blood glucose (p < 0.05) and 25% of the TyG index, which is used to estimate insulin resistance (p < 0.05), compared with the non-treated group. The oxidovanadium-sulfur compound is a promising antihyperglycemic therapeutic, including in cases aggravated by insulin resistance induced by glucocorticoid treatment.

IBPA a mutual prodrug of ibuprofen and acetaminophen alleviates inflammation, immune dysregulation and fibrosis in preclinical models of systemic sclerosis.

Systemic sclerosis (SSc) is a devastating autoimmune illness with a wide range of clinical symptoms, including vascular abnormalities, inflammation, and persistent and progressive fibrosis. The disease's complicated pathophysiology makes it difficult to develop effective therapies, necessitating research into novel therapeutic options. Molecular hybridization is a strategy that can be used to develop new drugs that act on two or multiple targets and represents an interesting option to be explored for the treatment of complex diseases. We aimed to evaluate the effects of a hybrid mutual prodrug of ibuprofen and acetaminophen (IBPA) in peripheral blood mononuclear cells (PBMC) isolated from SSc patients, and in an in vivo model of SSc induced in BALB/c mice by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. The mice were treated at the same time with daily intraperitoneal injections of IBPA (40 mg/kg). Pulmonary and skin fibrosis as well as immune responses were evaluated. IBPA significantly decreased the release of cytokines in PBMC culture supernatants from SSc patients after stimulation with phytohemagglutinin-M (IL-2, IL-4, IL-6, IL-10, IL-13, IL-17A, TNF and IFN-γ).In HOCl-induced SSc, IBPA treatment prevented dermal and pulmonary fibrosis, in addition to reducing CD4 + T and B cells activation and reversing the M2 polarization of macrophages in spleen cells, and inhibiting IFN-γ secretion in splenocyte cultures. These results show the anti-inflammatory and antifibrotic effects of IBPA in SSc and highlight the therapeutic potential of this mutual prodrug, providing support for future studies.

Resveratrol directly suppresses proteolysis possibly via PKA/CREB signaling in denervated rat skeletal muscle.

Although there are reports that polyphenol resveratrol (Rsv) may cause muscle hypertrophy in basal conditions and attenuate muscle wasting in catabolic situations, its mechanism of action is still unclear. Our study evaluated the ex vivo effects of Rsv on protein metabolism and intracellular signaling in innervated (sham-operated; Sham) and 3-day sciatic denervated (Den) rat skeletal muscles. Rsv (10-4 M) reduced total proteolysis (40%) in sham muscles. Den increased total proteolysis (~40%) in muscle, which was accompanied by an increase in the activities of ubiquitin-proteasome (~3-fold) and lysosomal (100%) proteolytic systems. Rsv reduced total proteolysis (59%) in Den muscles by inhibiting the hyperactivation of ubiquitin-proteasome (50%) and lysosomal (~70%) systems. Neither Rsv nor Den altered calcium-dependent proteolysis in muscles. Mechanistically, Rsv stimulated PKA/CREB signaling in Den muscles, and PKA blockage by H89 (50µM) abolished the antiproteolytic action of the polyphenol. Rsv reduced FoxO4 phosphorylation (~60%) in both Sham and Den muscles and Akt phosphorylation (36%) in Den muscles. Rsv also caused a homeostatic effect in Den muscles by returning their protein synthesis rates to levels similar to Sham muscles. These data indicate that Rsv directly inhibits the proteolytic activity of lysosomal and ubiquitin-proteasome systems, mainly in Den muscles through, at least in part, the activation of PKA/CREB signaling.

Crucial role of carbon monoxide as a regulator of diarrhea caused by cholera toxin: Evidence of direct interaction with toxin.

The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl- efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster.

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 µmol L-1, and 17.9 µg L-1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

(R)-ketamine attenuates neurodevelopmental disease-related phenotypes in a mouse model of maternal immune activation.

Infections during pregnancy are associated with an increased risk of neuropsychiatric disorders with developmental etiologies, such as schizophrenia and autism spectrum disorders (ASD). Studies have shown that the animal model of maternal immune activation (MIA) reproduces a wide range of phenotypes relevant to the study of neurodevelopmental disorders. Emerging evidence shows that (R)-ketamine attenuates behavioral, cellular, and molecular changes observed in animal models of neuropsychiatric disorders. Here, we investigate whether (R)-ketamine administration during adolescence attenuates some of the phenotypes related to neurodevelopmental disorders in an animal model of MIA. For MIA, pregnant Swiss mice received intraperitoneally (i.p.) lipopolysaccharide (LPS; 100 µg/kg/day) or saline on gestational days 15 and 16. The two MIA-based groups of male offspring received (R)-ketamine (20 mg/kg/day; i.p.) or saline from postnatal day (PND) 36 to 50. At PND 62, the animals were examined for anxiety-like behavior and locomotor activity in the open-field test (OFT), as well as in the social interaction test (SIT). At PND 63, the prefrontal cortex (PFC) was collected for analysis of oxidative balance and gene expression of the cytokines IL-1ß, IL-6, and TGF-ß1. We show that (R)-ketamine abolishes anxiety-related behavior and social interaction deficits induced by MIA. Additionally, (R)-ketamine attenuated the increase in lipid peroxidation and the cytokines in the PFC of the offspring exposed to MIA. The present work suggests that (R)-ketamine administration may have a long-lasting attenuation in deficits in emotional behavior induced by MIA, and that these effects may be attributed to its antioxidant and anti-inflammatory activity in the PFC.

The antihyperglycemic and hypolipidemic activities of a sulfur-oxidovanadium(IV) complex.

This study describes the synthesis, characterization, and biological activity of a new class of antidiabetic oxidovanadium(IV)-complexes with S2O2 coordination mode. The target complex 3,6-dithio-1,8-octanediolatooxidovanadium(IV), abbreviated as ([VIVO(octd)]), where octd = 3,6-dithio-1,8-octanediol, is formed from the reaction between the 3,6-dithio-1,8-octanediol and vanadyl sulfate (VIVOSO4). The effects of treatment with ([VIVO(octd)] on blood glucose, lipidic profile, body weight, food intake, water intake, urinary volume, glycogen levels, and biomarkers for liver toxicity were investigated using a streptozotocin (STZ)-induced diabetic Wistar rats model. The results have shown that the [VIVO(octd)] complex caused a significant decrease in blood glucose (247.6 ± 19.3 mg/dL vs 430.1 ± 37.6 mg/dL diabetic group, p < 0.05), triglycerides (TG, 50%) and very low-density cholesterol (VLDL-C, 50%) levels in STZ-diabetic rats after 3 weeks of treatment. The [VIVO(octd)] has shown antihyperglycemic activity in diabetic rats as well as a reduction in elevated lipid levels. Time-dependent studies using EPR and 51V NMR spectroscopy of [VIVO(octd)] were done in aqueous solutions to determine the complex stability and species present in the oral gavage solution used for complex administration. The spectroscopic studies have shown that the antidiabetic/hypolipidemic activity could be attributed to [VIVO(octd)], vanadium species resulting from redox processes, the hydrolysis of [VIVO(octd)] and its decomposition products, or some combination of these factors. In summary, the oxidovanadium(IV) complex containing the S2O2 donor ligand has desirable antidiabetic properties eliminating the symptoms of Diabetes mellitus and its comorbidities.

STAT6 controls the stability and suppressive function of regulatory T cells.

Signal transducer and activator of transcription 6 (STAT6) promotes tumorigenesis by decreasing the Forkhead box P3+ (Foxp3+) cell frequency allowing for the infiltration of inflammatory cells during the early stages of colitis-associated cancer (CAC). In this study, we dissected the role of STAT6 in the generation of inducible in vitro regulatory T cells (iTregs) and peripheral in vivo Tregs (pTregs) under inflammatory conditions. In in vitro assays, when STAT6 was lacking, iTregs preserved a stable phenotype and expressed high levels of Foxp3 and CD25 during long expansion periods, even in the presence of IL-6. This effect was associated with increased in vitro suppressive ability, over-expression of programmed death-1 (PD-1), CTLA-4, and Foxp3, and decreased IFN-γ expression. Furthermore, iTregs developed during STAT6 deficiency showed a higher demethylation status for the FOXP3 Treg-specific demethylated region (TSDR), coupled with lower DNA methyltransferase 1 (DNMT1) mRNA expression, suggesting that STAT6 may lead to Foxp3 silencing. Using a mouse model of CAC, the STAT6-/- pTregs expressed a more activated phenotype at the intestine, had higher suppressive capacity, and expressed more significant levels of PD-1 and latency-associated peptide of TGF-ß (LAP) associated with their ability to attenuate tumor development. These data suggest that STAT6 signaling impairs the induction, stability, and suppressive capacity of Tregs developed in vitro or in vivo during gut inflammation.

Acute and sub-acute toxicity study of ethanol extract from Nectandra leucantha Nees & Mart. (Lauraceae) barks.

Nectandra leucantha has been used in traditional medicine. Several metabolites isolated from N. leucantha extracts displayed immunomodulatory, antileishmanial properties, but the determination of the toxicological profile in mammals has not previously been performed. In this study, the ethanol extract from N. leucantha barks (EENl) was characterized by HPLC/HRESIMS. To study acute toxicity, female mice received EENl in a single dose of 100, 300, 1000, or 2000 mg/kg bw. Later, sub-acute toxicity was introduced in female and male mice by oral gavage at 100, 500 or 1000 mg/kg bw for 28 consecutive days. Hematological and biochemical profiles from the blood as well as histological analysis from the liver and kidney were performed. The HPLC/HRESIMS analysis of the EENl revealed the presence of six neolignans chemically related to dehydrodieugenol B. In the oral acute and sub-chronic studies, EENl did not produce in all doses evaluated any alteration in behavior, biochemical, hematological, body weight gain and food intake or sudden death in Swiss mice. In addition, histopathological data did not reveal any disturbance in liver and kidney morphology after 28 days of EENl treatment. Our results indicate that EENl at dosage levels up to 2000 mg/kg bw is non-toxic and can be considered safe for mammals.

Prevention of necrosis in ischemic skin flaps using hydrogel of Rhizophora mangle.

INTRODUCTION: Necrosis in ischemic cutaneous flaps (ISF) is a type of surgical failure more feared among surgical complications. Currently, synthetic drugs are applied during the treatment of necrosis in ISF and although several substances show improvement in viability, some require application at high systemic doses, which can produce important side effects. Therefore, the search for natural substances with fewer side effects is constant. The use of medicinal plants that stimulate angiogenesis is commonly mentioned in previous studies and in this case Rhizophora mangle L. (R. mangle) highlights that among its main compounds have tannins and flavonoids that are very chemically reactive in various biological activities. This study aimed to associate a natural hydrogel to the 5% extract of R. mangle and to evaluate its potential in the prevention of tissue necrosis in distal portions of ISF in rats, using the model proposed by Macfarlane, et al. (1965). METHODS: Ischemic skin flaps were made in the thin dorsal skin area of 28 Wistar rats and divided into 4 groups, group A: received only saline, group B where the aqueous extract of R. mangle was applied, group C received the 1.5% hydrogel of xanthan gum (XG) + placebo and group D was applied the hydrogel associated with 5% R. mangle extract. Morphometric analyses of the areas of tissue necrosis were performed from photographic records using the software Photoshop® and ImageJ®. In addition, 5 photomicrographs were taken from each histological sample of each animal for histomorphometric analysis that obtained the count of fibroblasts and blood vessels. RESULTS: The mean percentage of necrotic areas was: group (A) - 50,66%, group (B) - 40,49%, group (C) - 37,44% and group (D) - 34,25%. The statistical analysis, using the Kruskal-Wallis test, showed a significant difference (p < 0.001).

Antidiabetic properties of oral treatment of hexane and chloroform fractions of Morus nigra leaves in streptozotocin-induced rats.

Morus nigra L. has been widely used in Brazilian folk medicine for the treatment of diabetes. We evaluate the chemical composition and antidiabetic properties of the hexane (Hex-Mn) and chloroform (Chlo-Mn) fractions obtained by partition of the crude ethanolic extract from the leaves in rats. Chemical composition analysis of Hex-Mn and Chlor-Mn was performed by gas chromatography-mass spectrometry (CG-MS). In vivo and in vitro studies were carried out to compare the antidiabetic activities of the Hex-Mn and Chlor-Mn fractions. Most of the compounds identified in Hex-Mn were α-linolenic acid, stigmast-5-en-3-ol and linolenic acid ethyl ester, while in Chlor-Mn, stigmast-5-en-3-ol, palmitic acid and α-linolenic acid were mainly identified. Only Hex-Mn treatment reduced both fasting and postprandial hyperglycemia. Additionally, Hex-Mn preserved body weight gain, preserved the hepatic glycogen content, and also reduced the thiobarbituric acid reactive substances and nitrite levels, as well as restored the superoxide dismutase. Furthermore, digestion of complex carbohydrates and intestinal glucose absorption was prevented by Hex-Mn treatment. Our results suggest that the antidiabetic activity of Hex-Mn may be explained, at least in part, by the insulin sensitivity increase, antioxidant properties and reduction in carbohydrate absorption in the small intestine.

Non-clinical repeated dose 28-day oral toxicity, reproductive toxicity and cytotoxicity studies of the polar fraction of Parkinsonia aculeata aerial parts extract.

This study was aimed to evaluate toxicity in repeated doses for 28 days, reproductive toxicity and cytotoxicity of a polar fraction obtained from the hydroethanolic extract of Parkinsonia aculeata (PfrHEPA) in experimental models. To perform the toxicity test in repeated doses for 28 days, male and female Wistar rats were treated via orogastric for 28 days with PfrHEPA (35, 70 or 140 mg/kg) according to the guidelines established by the Organisation for Economic Co-operation and Development (OECD) number 407 (1995). For assessment, the impact of PfrHEPA on the reproductive output various parameters were measured, including maternal weight, no. of pregnant females, female fertility index (%), gestation lengthtime, implantation sites, litter size and placental index of test animals. The cytotoxicity of PfrHEPA was performed on the tumor lines NCI-H292 (human lung carcinoma), HL-60 (human promyelocytic leukemia) and HCT-116 (colorectal cancer). In the repeated dose toxicity test for 28 days, no mortality was observed in the male and female rats treated with PfrHEPA as well as morphological changes and biochemical and hematological parameters. In the reproductive toxicity test, no abnormalities were observed related to the toxicological parameters in both mothers and offspring. Regarding the cytotoxicity assay, the PfrHEPA fraction did not demonstrate significant cytotoxic effect on the cell lines analyzed. The present results suggest the use of PfrHEPA is safe and well tolerated in rats. Further studies are planned to identify and purify the active compounds for subsequent in vivo evaluation.

Safety assessment of Bauhinia cheilantha Bong. Steud leaves extract: acute, sub-acute toxicity, antioxidant, and antihemolytic evaluations.

Bauhinia cheilantha (Fabaceae), known popularly as pata-de-vaca and mororó has been largely recommended treating several diseases in folk medicine. However, information on safe doses and use is still scarce. The goal was to evaluate in-vitro antioxidant and antihemolytic and also acute and sub-acute toxicity effects of hydroalcoholic extract from B. cheilantha leaves (HaEBcl). The identification of the compounds in the HaEBcl was performed by ultra-performance liquid chromatography coupled with a diode array detector and quadrupole time-of-flight mass spectrometry. Antioxidant and hemolytic activity of HaEBcl was evaluated in vitro. To study acute toxicity, female mice received HaEBcl in a single dose of 300 and 2.000 mg/kg. Later, sub-acute toxicity was introduced in both female and male mice by oral gavage at 300, 1000, or 2000 mg/kg for 28 consecutive days. Hematological and biochemical profiles were created from the blood as well as from histological analysis of the liver. HaEBcl is rich in flavonoids (quercitrin and afzelin), has no hemolytic effects and moderate antioxidant effects in vitro. Acute toxicity evaluation showed that lethal dose (LD50) of HaEBcl was over 2000 mg/kg. Sub-acute toxicity testing elicited no clinical signs of toxicity, morbidity, or mortality. The hematological and biochemical parameters discounted any chance of hepatic or kidney toxicity. Furthermore, histopathological data did not reveal any disturbance in liver morphology in treated mice. Results indicate that HaEBcl has no hemolytic and moderate antioxidant effects in vitro. In addition, HaEBcl dosage levels up to 2000 mg/kg are nontoxic and can be considered safe for mammals.

Vasopressin and copeptin release during sepsis and septic shock.

Sepsis is defined as a potentially fatal organ dysfunction caused by a dysregulated host response to infection. Despite tremendous progress in the medical sciences, sepsis remains one of the leading causes of morbidity and mortality worldwide. The host response to sepsis and septic shock involves changes in the immune, autonomic, and neuroendocrine systems. Regarding neuroendocrine changes, studies show an increase in plasma vasopressin (AVP) concentrations followed by a decline, which may be correlated with septic shock. AVP is a peptide hormone derived from a larger precursor (preprohormone), along with two peptides, neurophysin II and copeptin. AVP is synthesized in the hypothalamus, stored and released from the neurohypophysis into the bloodstream by a wide range of stimuli. The measurement of AVP has limitations due to its plasma instability and short half-life. Copeptin is a more stable peptide than AVP, and its immunoassay is feasible. The blood concentrations of copeptin mirror those of AVP in many physiological states; paradoxically, during sepsis-related organ dysfunction, an uncoupling between copeptin and AVP blood levels appears to happen. In this review, we focus on clinical and experimental studies that analyzed AVP and copeptin blood concentrations over time in sepsis. The findings suggest that AVP and copeptin behave similarly in the early stages of sepsis; however, we did not find a proportional decrease in copeptin concentrations as seen with AVP during septic shock. Copeptin levels were higher in nonsurvivors than in survivors, suggesting that copeptin may work as a marker of severity or sepsis-related organ dysfunction.

Sepsis impairs the propagation of cortical spreading depression in rats and this effect is prevented by antioxidant extract.

Sepsis is a clinical syndrome with high morbidity and mortality. It is characterized by acute inflammatory response and oxidative stress, which is implicated in cerebral dysfunction. Murici (Byrsonimacrassifolia (L.) Kunth) is a fruit rich in antioxidant compounds, which could be an alternative to prevent damage to tissues induced by sepsis . Here, we evaluated the effects of sepsis on the propagation of cortical spreading depression (CSD) and oxidative stress, and tested the action of murici antioxidant extract in prevention against the effect of sepsis. Male Wistar rats (90-210 days, n = 40) were previously supplemented, orogastrically, with murici extract (150 mg/kg/day or 300 mg/kg/day), or an equivalent volume of the vehicle solution, for fifteen days. Then the animals were subjected to experimental sepsis through cecal ligation and perforation (CLP). Subsequently, CSD recordings were obtained and brain oxidative stress was evaluated. Sepsis decelerated CSD and increased the malondialdehyde (MDA) levels in the brain cortex of the animals. In contrast, septic rats that had been previously supplemented with murici antioxidant extract in doses of 150 and 300 mg/kg/day showed an increase in CSD propagation velocity, low levels of MDA and GSH/GSSG ratio and an increase of superoxide dismutase (SOD) activity, regardless of the dose tested. Our results demonstrate that sepsis affects brain excitability and that this effect can be prevented by murici antioxidant extract. The effects of sepsis and/or murici extract on CSD may be due to the oxidative state of the brain.

Hexane fraction from Brazilian Morus nigra leaves improved oral carbohydrate tolerance and inhibits α-amylase and α-glucosidase activities in diabetic mice.

Morus nigra, popularly known as mulberry, has been traditionally used as anti-diabetic herbal medication. This study focused on hexane fraction from Brazilian M. nigra leaves (Hex-Mn) effects on digestion and absorption of carbohydrate in diabetic mice. The high-performance liquid chromatography (HPLC) analysis was performed, and showed the presence of flavonoids isoquercetin and kaempferol-3-O-rhamnoside. Hex-Mn did not alter oral glucose tolerance test; however, it prevented hyperglycemia in oral sucrose and starch tolerance test in diabetic mice. Also, Hex-Mn was more efficient to inhibit the α-glucosidase, showing lower inhibitory effect on α-amylase activity in vitro. The results suggest that Hex-Mn may delay the carbohydrate digestion, but not glucose transport through brush border membrane of the intestine, which contribute with reduction in postprandial hyperglycemia in mice. Hex-Mn has antihyperglycemic effect by attenuating the carbohydrate digestion in diabetic mice, which could be explained, at least in part, by the presence of isoquercetin and kaempferol-3-O-rhamnoside.

Spondias tuberosa inner bark extract exert antidiabetic effects in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM) is one of the most important medical emergencies of the 21st century. However, commercially available oral drugs with antidiabetic properties have been limited because of potential side effects, such as: hypoglycemia, weight gain, hepatic dysfunction and abdominal discomfort. As well as antidiabetic drugs, many types of medicinal herbal supplements are utilized as alternative treatments for DM and related comorbidities. Spondias tuberosa Arruda (Anacardiaceae), popularly known as "umbu", has been used in traditional medicine to treat a vast range of diseases, including DM, infections, digestive disorders, diarrhea and menstrual abnormalities. AIM OF THE STUDY: This study evaluated the effect of the hydroethanolic extract of the inner stem bark of Spondias tuberosa (EEStb) in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced in rats by a single injection of STZ (40 mg/kg i.p.). Diabetic rats were treated with 250 mg/kg or 500 mg/kg of the EEStb for 21 days. Water intake, urinary volume, body weight, as well as biochemical parameters, such as cholesterol total (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), hepatic and muscle glycogen urea, alanine and aspartate aminotransferase, total protein, albumin, and glucose blood levels, were analyzed. We also determined the hepatic antioxidant state, as well as both of insulin and glucose tolerance. RESULTS: The extract was evaluated by HPLC, and the major components of EESTb were identified (i.e. gallic acid and quercetin). The 500 mg/kg dosage of EEStb significantly decreased fasting blood glucose and post-prandial glucose. The EEStb also reduced urinary volume, food and water intake, as well as decreased body weight gain. Diabetic rats that received EEStb had a lower loss of muscle mass and white adipose tissue. Additionally, EEStb improved the urinary excretion of urea and glucose. The extract significantly decreased triglycerides, total cholesterol and VLDL in diabetic rats. However, no significant effect was observed on the levels of total and HDL cholesterol. EEStb treatment prevented hepatotoxic diabetic-induced, improved GSH:GSSG ratio, SOD and CAT activity as well as reduced nitrite and TBARs levels. CONCLUSIONS: Our results demonstrate that EEStb has antioxidant and hepatoprotective effects as well as improves insulin sensibility in diabetic rats. This indicates that S. tuberosa could be a potential resource for alternative therapies in the treatment of hyperglycemic conditions. These results also support the use of EEStb in ethnomedicine for the management of diabetes.

Can coconut oil and treadmill exercise during the critical period of brain development ameliorate stress-related effects on anxiety-like behavior and episodic-like memory in young rats?

OBJECTIVE: Virgin coconut oil (CO) and treadmill exercise have been reported to improve memory performance in young rats. CO has also been associated with antistress properties in young, stressed mice. Therefore, in this study we aimed to investigate whether CO and treadmill exercise could synergistically ameliorate the effects of chronic stress on anxiety-like behavior and episodic-like memory in young rats. METHODS: The rats received CO and were exercised (Ex) from the 15th to the 45th day of life. The animals were supplemented with CO (10 mL kg-1 day-1) or a vehicle (V, distilled water and 0.009% Cremophor) via oral gavage. The Ex animals were placed for 30 min day-1 on a treadmill, with the speed gradually increasing from the first week to the last. From the 46th to the 54th postnatal day, with the exception of the 51st and the 52nd day, all rats were subjected to restraint stress. Afterwards, all rats underwent the open-field test to evaluate locomotor activity and anxiety-like behavior. To evaluate episodic-like memory, all animals underwent tests to recognize object identity and special location. Lastly, lipid profile and murinometric parameters were evaluated. RESULTS: A two-way ANOVA test followed by a Tukey test demonstrated that the CO&Ex group explored more of the unprotected central area of the OFT (27.04 ± 4.03 s, p < 0.01), when compared to the control group (15.36 ± 2.54 s). CO&Ex spent more time exploring the novel location of the object (71.62 ± 3.04%, p < 0.01), when compared to the control group (58.62 ± 2.48%). DISCUSSION: CO and exercise during lactation can ameliorate the effects of stress on anxiety-like behavior and episodic-like memory in young rats.

Evaluation of embryotoxic and embryostatic effects of the aqueous extract of Rhizophora mangle and tannic acid on eggs and larvae of Aedes aegypti.

Rhizophora mangle is an abundant plant in mangroves and tannic acid is a polyphenol produced by the secondary metabolism of plants. The aim of the study was to evaluate the embryotoxic and embriostatic effects of the aqueous extract of R. mangle and synthetic tannic acid on eggs and larvae of Aedes aegypti. A. aegypti eggs were exposed in duplicate at concentrations of 250, 500, 750 and 1000 µg/mL of extract and tannic acid for a period of 14 days. Mineral water was used as a negative control. The eggs were observed and counted in a stereomicroscope (1.2x). In all extract concentrations there was stimulation in hatching in relation to the control, but only in concentration of 750 mg/mL it was statistically significant. In tannic acid (250µg/ml) there was significant stimulus in hatching, but in 500, 750 and 1000 µg/mL there was significant inhibition. All concentrations of aqueous extract and tannic acid on larvae showed embryotoxic and embryostatic effects when compared to the control. The aqueous extract of R. mangle showed effect on hatching of A. aegypti eggs and synthetic tannic acid showed embryotoxic and embryostatic effects. On larvae, both the aqueous extract as tannic acid showed embryotoxic and embryostatic effects.

Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats.

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats.