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.

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'-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.

Alkaloids Pharmacological Activities - Prospects for the Development of Phytopharmaceuticals for Neurodegenerative Diseases.

The study of natural substances has increased in recent years in the search for compounds with pharmacological properties that can be used for the development of new drugs. The alkaloids, substances extracted natural sources, show promising pharmacological activities, including pharmacological activities for the treatment of neurodegenerative diseases such as Alzheimer's disease, whose treatment is based on the use of various drugs. Thus, the article aims to a technological prospecting of alkaloids that presented important properties in the treatment of neurodegenerative diseases, namely, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties. A literature review was conducted in the databases PubMed, Science Direct, Scopus, Scielo and Google Academics using the following key words: alkaloids, pharmacology, neurodegenerative diseases, cholinesterase inhibitors, antidepressants, anti-inflammatories, antioxidant and anxiolytic. Articles, dissertations and theses published between 2003 and 2015 were selected. Several studies showed through in vitro of in vitro and/or in vivo methods that many alkaloids extracted from plants showed anticholinesterase, antioxidant, anxiolytic, anti-inflammatory and antidepressant properties in the treatment of symptoms and progression of certain diseases such as Alzheimer's disease.

Investigation of biological activities of dichloromethane and ethyl acetate fractions of Platonia insignis Mart. seed.

Platonia insignis Mart., a native species of the Brazilian Amazon more commonly known as bacuri, is a member of the Clusiaceae family. In this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from P. insignis seed ethanolic extract using different experimental models. Our results demonstrate in vitro antioxidant effects, by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1,1-diphenyl-2-picryl-hydrazyl assays, as well as in vivo effects in antioxidant-defective Saccharomyces cerevisiae strains to both fractions. Toxicity was evaluated against the micro-crustaceous Artemia salina Leach. and promastigote Leishmania amazonensis. The dichloromethane fraction was the most active fraction evaluated on A. salina and promastigote L. amazonensis (IC(50)  = 24.89 µg/mL and 2.84 µg/mL, respectively). In addition, a slight cytotoxicity was observed in mammalian V79 cells using ethyl acetate and dichloromethane fractions with MTT assays. Both fractions displayed genotoxicity up to 25 µg/mL (dichloromethane) and 10 µg/mL (ethyl acetate) in V79 cells, as evaluated by the alkaline comet assay. Thus, in this study, we demonstrate for the first time that ethyl acetate and dichloromethane fractions from P. insignis seeds display antioxidant effects, a toxic effect against A. salina and L. amazonensis and induce genotoxicity in V79 mammalian cells. The observed activities can be attributed to the phenolic compounds present in these fractions and to the presence of xanthones (alpha- and gamma-mangostin).