Anxiolytic-like effects of phytol: possible involvement of GABAergic transmission.

Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75 mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble-burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75 mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.

Avaliação da toxicidade aguda e das alterações histopatológicas em camundongos tratados com fitol / Assessment of acute toxicity and histopathological changes in mice treated with phytol

O fitol, (3,7,11,15-tetrametilhexadec-2-en-1-ol), é um diterpeno pertencente ao grupo dos álcoois acíclicos insaturados de cadeia longa e ramificada. É um componente da molécula da clorofila, presente em folhas verdes de várias plantas medicinais. Entretanto, pouco é descrito na literatura sobre os possíveis efeitos toxicológicos produzidos pelo fitol. O objetivo do nosso estudo foi avaliar a toxicidade aguda do fitol, após administração intraperitoneal para determinação da dose letal 50% (DL50) e os efeitos sobre os parâmetros bioquímicos, hematológicos e histopatológicos no hipocampo e corpo estriado de camundongos adultos tratados com fitol nas doses de 25, 50 e 75 mg/kg. Os testes para determinação do grau de toxicidade aguda, bem como a investigação da DL50, revelou que o valor é aproximadamente 1153.39 mg/kg. Os camundongos tratados com as doses selecionadas do fitol a partir da DL50 apresentaram todos os parâmetros hematológicos dentro da faixa de referência, observando-se alterações nos valores dos linfócitos. Por sua vez, a maioria dos valores dos parâmetros bioquímicos diminuiu em todas as doses testadas (p<0,05). Em nosso estudo, apenas os animais tratados com fitol na dose de 75 mg/kg demonstraram uma discreta vacuolização no corpo estriado e um discreto comprometimento caracterizado por vacuolização no hipocampo em apenas um dos animais. Nossos resultados indicam que o tratamento com fitol não produz alterações hematológicas, bioquímicas e histopatológicas cerebrais em camundongos. O estudo toxicológico pré-clínico com fitol demonstrou que o produto avaliado possui discreta toxicidade aguda por via intraperitoneal, sendo estes dados uma contribuição para pesquisas com compostos obtidos de plantas medicinais com potencial farmacológico. Porém, ressalta-se a necessidade de futuras pesquisas que possibilitem comparar os resultados em outras vias, bem como para realizar análises anatomopatológicas dos animais tratados com fitol, para assegurar o uso seguro deste diterpeno.

Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol) is a diterpene belonging to the group of acyclic unsaturated long-chain branched alcohols. It is a component of the chlorophyll molecule, present in green leaves of various medicinal plants. However, there is little in the literature about the possible toxic effects produced by phytol. The aim of our study was to assess the acute toxicity of phytol after intraperitoneal (ip) administration, by determining its 50% lethal dose (LD50) and effects on biochemical parameters, hematology and the histopathology of the hippocampus and corpus striatum of adult mice treated with doses of 25, 50 and 75 mg/kg phytol. The acute toxicity tests and investigation of the LD50 revealed its value to be approximately 1153.39 mg/kg. Mice treated with sublethal doses of phytol based on the LD50 showed all hematological parameters within their reference ranges, with small changes in the lymphocyte count. In turn, most of the biochemical parameters decreased at all doses tested (p<0.05). In our study, only those animals treated with phytol at a dose of 75 mg/kg showed slight vacuolation in the corpus striatum and a slight impairment characterized by vacuolation in the hippocampus in one animal. Our results indicate that treatment with phytol produces no hematological, biochemical or brain histopathological changes in the mice. The preclinical toxicological study with phytol showed that it has slight acute toxicity when injected ip. These data contribute to research on natural compounds obtained from medicinal plants with pharmacological potential. However, we emphasize the need for future research to enable results obtained by other routes to be compared, as well as to conduct pathological analysis in animals treated with phytol, to ensure the safe use of this diterpene.

Superoxide dismutase and catalase activities in rat hippocampus pretreated with garcinielliptone FC from Platonia insignis.

CONTEXT: Platonia insignis Mart. (Clusiaceae), commonly known as "bacuri," is a timber and fruit native species of the Brazilian Amazon. Some plants of the Clusiaceae family have their pharmacological properties associated with the presence of xanthone and polycyclic polyprenylated acylphloroglucinols derivatives, which have antioxidant and anticarcinogenic activities. OBJECTIVE: The aim of this study was to assess the in vivo potential of extracts, fractions, and garcinielliptone FC isolated from of Platonia insignis seeds as a natural antioxidant. MATERIALS AND METHODS: Male Wistar rats (250-280 g; 2 months old) were treated with Tween 80 0.05% dissolved in 0.9% saline (i.p, vehicle - control group), ethanol extract (EE), hexane extract (HE), dichloromethane fraction (DMF), ethyl acetate fraction (EAF), and garcinielliptone FC (GFC) isolated from P. insignis at doses 2 mg/kg (i.p.). All groups were observed for 24 h after the treatment. The antioxidant enzymatic activities [superoxide dismutase (SOD) and catalase (CAT)] were measured using spectrophotometric methods. RESULTS: There were no marked alterations in SOD and CAT activities in rat hippocampus after pretreatment with EE, HE, DMF, EAF, and GFC. However, the pretreatment with GFC induced a significantly increase of 13, 17, 19, and 13% in SOD activities when compared to EE, HE, DMF, or EAF groups, respectively. DISCUSSION AND CONCLUSION: Our findings strongly support the hypothesis that GFC isolated from P. insignis has a significant potential to be used as a natural antioxidant agent probably due to the modulation of enzymatic activity of hippocampal SOD.