Anticonvulsant, Anxiolytic and Antidepressant Properties of the ß-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems.

BACKGROUND: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. METHODS: This study evaluated the neurobehavioral effects of ß-CBP using the open field test, rota- rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. RESULTS: The results demonstrated that the neuropharmacological activities of ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of ß-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500-750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.

Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection.

Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoniex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.

Bergenin from Peltophorum dubium: Isolation, Characterization, and Antioxidant Activities in Non-Biological Systems and Erythrocytes.

BACKGROUND: Bergenin, a compound derived from gallic acid, is a secondary metabolite of the plant Peltophorum dubium (Spreng.) Taub. OBJECTIVE: In this study, we aimed to characterize the ability of bergenin to eliminate the radicals in non-biological systems. METHODS: We evaluated bergenin's ability to protect erythrocytes from oxidative damage in a biological system. We have elucidated bergenin structure using nuclear magnetic resonance, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry. We then evaluated its antioxidant capacity in vitro against DPPH•, ABTS•+, hydroxyl radicals, and nitric oxide, and determined its ability to transfer electrons owing to its reduction potential and ability to chelate iron. We also evaluated its protective capacity against oxidative damage produced by AAPH in erythrocytes, its hemolytic properties, its ability to inhibit hemolysis, and its ability to maintain intracellular reduced glutathione homeostasis. RESULTS: Bergenin concentrations between 0.1 and 3mM significantly (p < 0.05) and dose dependently decreased formation of ABTS•+, DPPH•, nitrite ions, OH•, reduced formation ferricyanide, ferrozine-Fe2+complex, inhibited AAPH-induced oxidative hemolysis of erythrocytes, raised GSH levels in the presence of AAPH, inhibited AAPH-induced lipid peroxidation in erythrocytes. CONCLUSION: Bergenin may represent a novel alternative antioxidant, with potential applications in various industries, including drugs, cosmetics, and foods.

Evaluation of Antioxidant Activity of Phytol Using Non- and Pre-Clinical Models.

BACKGROUND: Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol; PHY), the alcoholic diterpenoid is particularly interesting due to its diverse activities found in literature. This study evaluated in vitro and in vivo antioxidant capacity of PHY. METHODS: We conducted DPPH• (2,2-diphenyl-1-picrylhydrazyl) and ABTS•+ (2,2&#039;-azino-bis(3- ethylbenzthiazoline-6-sulphonic acid)) radical scavenging tests as in vitro, while Saccharomyces cerevisiae test as in vivo. For in vitro tests, trolox and for in vivo test hydrogen peroxide (H2O2) were taken as standard and stressor, respectively. Additionally, we measured the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), lipid peroxidation (LP) and nitrite (NO2 -) contents in mouse hippocampus taking 0.05% Tween 80 dissolved in 0.9% saline (0.25 ml) and ascorbic acid (250 mg/kg; AA) as vehicle and standard, respectively. PHY was administered at doses 25, 50 and 75 mg/kg. In the latter case, all the treatments were administered via intraperitoneal (i.p.) route. RESULTS: PHY at 7.2 µg/ml exhibited 59.89 ± 0.73% and 62.79 ± 1.99% scavenging capacity of DPPH• and ABTS•+, respectively. In S. cerevisiae strains, PHY showed prominent protective effects. Moreover, in Swiss mouse hippocampus; PHY reduced the LP and NO2 - contents, while increased in GSH, SOD and CAT activities. CONCLUSION: PHY exerted antioxidant potential in our current non- and preclinical test systems and can be a good candidate for the development of treatments of oxidative stress mediated diseases.

In vitro effects of arylhydrocoumarin on free radicals and oxidative stress in erythrocytes and Saccharomyces cerevisiae.

Neoflavonoids comprise a group of natural compounds with varied chemical structures and promising pharmacological properties, including antioxidant capacity. This work describes an evaluation of the in vitro antioxidant capacity of a new coumarin derivative, i.e., 7-acetoxy-4-aryl-3,4-dihydrocoumarin, in terms of its ability to quench the 2,2- diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), hydroxyl (OH•) and superoxide anion (O2(•-)) radicals, as well as its capacity to initiate electron transfer by reducing potential and inhibit lipid peroxidation by TBARS (thiobarbituric acid reactive substances) method. In addition, the antioxidant capacity of 7-acetoxy-4-aryl-3,4-dihydrocoumarin was evaluated against oxidative damage induced by hydrogen peroxide in erythrocyte suspensions and S. cerevisiae strains. In all methodologies investigated, high antioxidant capacities above 65% were demonstrated by 7-acetoxy-4-aryl-3,4-dihydrocoumarin against the DPPH(•), ABTS(•+), OH(•) and O2(•-) radicals. The ability of 7-acetoxy-4-aryl-3,4-dihydrocoumarin to inhibit oxidative damage induced by hydrogen peroxide in erythrocytes and S. cerevisiae strains demonstrates the importance of this compound in the protection against oxidative stress at the cellular level. Thus, the results obtained in this study suggest that 7-acetoxy-4-aryl-3,4-dihydrocoumarin can assist the development of new antioxidant products for possible use in the prevention or reduction of diseases related to oxidative stress.

Mikania glomerata: Phytochemical, Pharmacological, and Neurochemical Study.

The present study primarily aims to identify the relative density and the fatty acids (methyl esters) content present in the standardized ethanol extract of leaves of M. glomerata (EPMG). Meanwhile, in a second moment, this study evaluated the effects of the EPMG on the levels of amino acids in the hippocampus, and the mechanism of sedative and anxiolytic action. Adult mice were treated with doses of 200, 300, and 400 mg/kg and evaluated in open field, elevated plus-maze, light dark, and rotarod tests. Moreover, in the behavioral tests diazepam (GABAergic anxiolytic, 2 mg/kg) as positive control and flumazenil (GABA antagonist, 2.5 mg/kg) were used to identify mechanism of sedative and anxiolytic action produced by EPMG. The EPMG is constituted by the following compounds: methyl cinnamate, 2H-1-benzopyran-2-one, (2-hydroxyphenyl)methyl propionate, (Z)-methyl-hexadec-7-enoate, methyl hexadecanoate, hexadecanoic acid, (Z)-methyl-octadec-9-enoate, octadecanoic acid, and squalene. This extract demonstrated anxiolytic effects, which may be mediated by GABAergic system, and was able to increase GABA levels and reduce of glutamate and aspartate concentrations in mice hippocampus, which can directly and/or indirectly assist in their anxiolytic effect. Although more studies are needed, the EPMG could represent an interesting therapeutical strategy in the treatment of anxiety.

Antischistosomal activity of the terpene nerolidol.

Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils of several plants, is found in many foods and was approved by the U.S. Food and Drug Administration. In this study we analysed the in vitro antiparasitic effect of nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2 and 62.5 µM reduced the worm motor activity and caused the death of all male and female schistosomes, respectively. In addition, confocal laser scanning microscopy revealed morphological alterations on the tegument of worms such as disintegration, sloughing and erosion of the surface, and a correlation between viability and tegumental damage was observed. In conclusion, nerolidol may be a promising lead compound for the development of antischistosomal natural agents.