Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts.

Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases.

Neuroprotective effects of valproic acid on brain ischemia are related to its HDAC and GSK3 inhibitions.

Valproic acid (VA) is an antiepileptic that is also used for the treatment of bipolar disorders. The objective was to evaluate the neuroprotective effects of VA on a brain ischemia model. The groups of male Wistar rats were: SO (sham-operated), ischemic and ischemic treated with VA (25, 50 and 100 mg/kg, p.o.). After anesthesia with ketamine and xilazine, the animals were subjected to clamping of carotid arteries (30 min) and reperfusion. Except for the carotid clamping, the SO group was submitted to the same procedure. On the 7th day, the animals were behaviorally evaluated, euthanized and had their brain dissected for neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and Tukey as the post hoc test. The results showed that VA reversed partly or completely the behavioral (locomotor activity and memory deficits), neurochemical (striatal DA and DOPAC levels, brain nitrite and lipid peroxidation) and immunohistochemical alterations (iNOS, COX-2, HDAC and GSK3) observed in the untreated ischemic group. VA neuroprotective effects are probably related to its anti-inflammatory and antioxidant properties, as well as to HDAC and GSK3 inhibitory effects. These findings stimulate translational studies focusing on VA as a neuroprotective drug to be potentially used in the clinic for several neurological conditions.

Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses.

In the present study, we evaluated omega-3 polyunsaturated fatty acid (PUFA) (consisting of 20:5n-3 and 22:6n-3) properties on inflammation and nociception. Among the in vivo tests, writhing, formalin, and hot plate tests were conducted in mice, and carrageenan-induced paw edema, peritonitis, and Hargreaves tests were performed in rats. Following the carrageenan-induced edema, immunohistochemistry for tumor necrosis factor-α (TNF-α) was also carried out. We found that omega-3 PUFA treatment significantly decreased acetic acid-induced abdominal contortions as well as the first and second phases of the formalin test, which were reversed by naloxone. The carrageenan-induced rat paw edema was significantly reduced, along with neutrophil migration to the peritoneal cavity in the omega-3 PUFA treatment. In addition, there was a decrease in TNF-α immunostained cells in the inflamed paw with the omega-3 treatment compared with no omega-3. Withdrawal threshold in response to the thermal stimulation was significantly increased by the omega-3 treatment in the Hargreaves and hot plate tests. The in vitro studies (myeloperoxidase, lactate dehydrogenase, MTT cell viability and lipid peroxidation assays) were performed in human neutrophils. These studies showed that omega-3 treatment significantly decreased myeloperoxidase release, presented no cytotoxicity, and did not alter lipid peroxidation. Our study suggests that omega-3 PUFA anti-inflammatory and antinociceptive actions may involve inhibition of cyclooxygenases and microglial activation, leading to a reduced release of proinflammatory cytokines such as TNF-α, among other factors. The omega-3 PUFAs are potential candidates used alone or in combination with conventional nonsteroidal anti-inflammatory drugs, for the treatment of diseases where inflammation plays an important role.

Coumarin effects on amino acid levels in mice prefrontal cortex and hippocampus.

Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.