Purple pitanga extract (Eugenia uniflora) attenuates oxidative stress induced by MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely used due to its specific and reproducible neurotoxic effect on the nigrostriatal system, being considered a convenient model of dopaminergic neurodegeneration to study interventions therapeutics. The purple pitanga (Eugenia uniflora) is a polyphenol-rich fruit with antioxidant and antidepressant properties, among others. Therefore, this study investigated the effect of purple pitanga extract (PPE) on acute early oxidative stress induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats. Male Wistar rats were pre-treated orally with PPE (1000 mg/kg) or vehicle. After 24 h, MPTP (0.1 mg/10µL/nostril) or vehicle was administered bilaterally into the animal's nostrils, and 6 h later, the olfactory bulb (OB), striatum (ST), and substantia nigra (SN) were collected to evaluate the oxidative stress parameters. Our findings revealed that OB and SN were the most affected areas after 6 h of MPTP infusion; an early increase in reactive oxygen species (ROS) levels was observed, while pretreatment with a single dose of PPE prevented this increment. No differences in thiobarbituric acid reactive species (TBARS) and 3-nitrotyrosine (3-NT) formation were observed, although 4-hydroxy-2-nonenal (4-HNE) levels increased, which is the most toxic form of lipid peroxidation, in the MPTP group. The PPE pretreatment could prevent this increase by increasing the NPSH levels previously decreased by MPTP. Furthermore, PPE prevents the Na+/K + ATPase strongly inhibited by MPTP, showing the neuroprotective capacity of the PPE by inhibiting the MPTP-generated oxidation. Thus, we demonstrated for the first time the antioxidant and neuroprotective effects of PPE against the early MPTP neurotoxicity.

Aqueous Bark Extract of Ceiba speciosa (A. St.-Hill) Ravenna Protects against Glucose Toxicity in Caenorhabditis elegans.

Plants are widely used in folk medicine because of their pharmacological properties. Ceiba speciosa, popularly known as paineira-rosa or tree-of-wool, is a species found in the Northwest of Rio Grande do Sul, being native of the upper Uruguay River, Brazil. The tea obtained from the stem bark is employed in folk medicine to reduce cholesterol, triacylglycerides, and glucose levels. However, there are no studies in the literature proving its efficacy or the safety of its use. For this study, we used Caenorhabditis elegans as an animal model considering its advantages for risk assessment and pharmacological screenings. For the toxicological tests, C. elegans N2 (wild type) was treated with the aqueous extract of the stem bark of C. speciosa (ECE) at the first larval stage (L1) at concentrations of 5, 25, 50, and 250 µg/mL. To evaluate biological activities, we challenged the extract for oxidative stress resistance in the presence of paraquat (0.5 mM), H2O2 (1 mM), and against glucose-induced toxicity. Our results demonstrated that ECE did not alter survival rate, pharyngeal pumping, and reproduction of the nematodes. The extract was not able to protect the nematodes against the toxicity induced by prooxidants. Notably, ECE protected against glucotoxicity by increasing worms' life span and by reducing glucose levels. On the other hand, ECE treatment did not reduce lipid accumulation induced by exogenous glucose feeding, as observed in worms which lipid droplets were tagged with GFP. Based on our results, we believe that the extract is indeed promising for further studies focusing on carbohydrates metabolism; however, it needs to be carefully evaluated since the extract does not seem to modulate lipid accumulation.

Lipid reducing potential of liposomes loaded with ethanolic extract of purple pitanga (Eugenia uniflora) administered to Caenorhabditis elegans.

The ethanolic extract obtained from purple pitanga fruit (Eugenia uniflora - PPE) has been previously described by its potential to reduce lipid accumulation in vitro. In this study, we aimed to study this potential in vivo using Caenorhabditis elegans as animal model. Considering the low pH of the extract, its hydrophilic characteristic, its absorption by the medium where the worms are cultivated and the need of a chronic exposure in the worms solid medium, we have loaded liposomes with PPE and investigated its potential for oral administration. Following 48 h exposure to the PPE-loaded liposomes on worms nematode growth medium, we did not observe any toxic effects of the formulation. Under high cholesterol diet, which increased worms total lipid and also triacylglycerides levels, liposomes containing PPE were able to significantly attenuate these alterations, which could not be observed when worms were treated with free PPE. Furthermore, we could evidence that liposomes were ingested by worms through their labelling to uranin fluorescence dye. Through total phenolic compounds quantification, we estimated an entrapment efficacy of PPE into liposomes of 87.7%. The high levels of phenolic compounds present in PPE, as previously described by our group, indicate that these antioxidants may interfere in worms lipid metabolism, which may occur through many and intricated mechanisms. Although the use of conventional liposomes for human consumption may not be pragmatic, its application for oral delivery of a hydrophilic substance in C. elegans was absolutely critical for our experimental design and has proven to be efficient.

(p-ClPhSe)2 stabilizes metabolic function in a rat model of neuroendocrine obesity induced by monosodium glutamate.

Obesity is a chronic and complex medical condition characterized by excessive fat accumulation and its complications include metabolic syndrome, diabetes and chronic inflammation. The aim of this study was to expand the knowledge about p-chloro-diphenyl diselenide (p-ClPhSe)2 effects on enzymes and proteins involved in the metabolism of lipids and carbohydrates in a model of neuroendocrine obesity induced by MSG. Male Wistar rats were treated during the first ten postnatal days with MSG (4 g/kg, s.c.) and received (p-ClPhSe)2 (10 mg/kg, i.g.) from 90th to 97th postnatal day. The hypothalamic function, insulin resistance and other biochemical parameters were determined in the rat blood, liver and skeletal muscle. The MSG administration induced hypothalamic neurotoxicity accompanied by metabolic disorders, including obesity, a transient insulin resistance, and metabolic alterations, demonstrated in the blood, liver and skeletal muscle, and lipotoxicity, characterized in the liver and skeletal muscle. The metabolic disorders in the liver and skeletal muscle were accompanied by the decrease in AMPK phosphorylation and activation of Akt. (p-ClPhSe)2 restored most of metabolic parameters altered by MSG administration in rats. The hypothalamic neurotoxicity induced by MSG was accompanied by metabolic disorders in rats, which were regulated by (p-ClPhSe)2.

Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age-Related Changes in the Hepatic Metabolism of Rats.

Aging is characterized by a widespread loss of homeostasis in biological systems and is accompanied by pathophysiological changes including the liver injury. The aim of the present study was to investigate the effects of the combined therapy with swimming exercise (20 min session, 5 days/week during 4 weeks) and a diet supplemented with 1 ppm of (PhSe)2 on the hepatic metabolic alterations caused by aging in rats. In this study, male old Wistar rats had an increase in the epididymal fat relative weight, disturbances in the activities of hepatic enzymes associated to the glucose homeostasis, higher hepatic triglyceride content and higher activity of the plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The combined therapy normalized the activities of glucose-6-Pase and tyrosine aminotransferase, gluconeogenic enzymes, increased the hepatic glycogen content and was effective against the increase in the hepatic triglycerides content, without altering the activities of hexoquinase, and citrate synthase. Moreover, the combined therapy normalized the activities of AST and ALT, indicating a hepatoprotective effect. The combined therapy with swimming exercise and a diet supplemented with 1 ppm of (PhSe)2 contributed to the hepatic glucose homeostasis in old rats. Nevertheless, more studies are needed to investigate the possible mechanisms of action behind these effects. J. Cell. Biochem. 118: 1574-1582, 2017. © 2016 Wiley Periodicals, Inc.

Selective inhibition of MAO-A activity results in an antidepressant-like action of 2-benzoyl 4-iodoselenophene in mice.

Depression is a leading cause of disability worldwide. For this reason, the aim of this study was to investigate the possible antidepressant-like activity of 2-benzoyl-4-iodoselenophene (C17H11IOSe), a selenophene compound, in two well-consolidated behavioral assays for screening antidepressant activity (forced swimming test and tail suspension test) in mice. In order to investigate the mechanism of action of C17H11IOSe, it was investigated the activities of cerebral enzymes: monoamine oxidase MAO A and B and Na+, K+ ATPase, and if an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA) (100mg/kg) blocks the antidepressant-like effect of C17H11IOSe. Swiss mice received (C17H11IOSe) (5-50mg/kg) or canola oil by the intragastric (i.g.) route before behavioral tests. The results showed that C17H11IOSe at dose range of 5-50mg/kg decreased immobility time in the tail suspension test. In the forced swimming test, C17H11IOSe reduced the immobility time at the doses of 10 and 50mg/kg. C17H11IOSe differently affected the cerebral cortical Na+, K+ ATPase; the effects on this enzyme were dependent of the dose tested. At a dose of 10mg/kg, the compound increased Na+, K+ ATPase activity, while the activity was inhibited at a dose of 50mg/kg. pCPA blocked the antidepressant-like action of C17H11IOSe in mice. Therefore, C17H11IOSe (5-50mg/kg) selectively inhibited MAO-A activity in cerebral cortices of mice. The modulation of serotonergic system contributed to the antidepressant-like action of C17H11IOSe in mice.