Involvement of monoaminergic systems in the antidepressant-like properties of Lafoensia pacari A. St. Hil.

ETHNOPHARMACOLOGICAL RELEVANCE: Lafoensia pacari A. St.-Hil. (Lythraceae), known popularly as "pacari" or "mangaba-brava" is popularly used in the state of Goiás, Brazil. The stem bark or leaves are used to treat cancer, gastric disorders, inflammation and as a tonic to treat loss of enthusiasm. AIM OF THE STUDY: Previous results suggest that the ethanol:water 7:3 extract of the stem bark of L. pacari (PEx) has antidepressant-like activity in male mice. Our aim was to perform the PEx׳s bioguided fractionation and evaluate the monoaminergic system involvement in the antidepressant effect as well as progress in the study of L. pacari mechanism of action. MATERIAL AND METHODS: Mice (30-35g) orally treated (24, 5 and 1h) with PEx (100, 300 or 1000mg/kg), chloroform (ChloF-70mg/kg), ethyl acetate (180mg/kg), n-butanol (370mg/kg) and aqueous (1g/kg) fractions were submitted to the forced swimming test. To assess the mechanism of action, different groups of mice were pretreated with p-chlorophenylalanine (PCPA-100mg/kg, 4 days, i.p.) and alpha-methyl-p-tyrosine (AMPT-100mg/kg, 4h, i.p.) to assess the involvement of serotoninergic and catecholaminergic systems in the ChloF effects, respectively. A putative in vitro inhibition of monoamine oxidase (MAO) activity as well as the ex vivo hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Phytochemical screening, spectroscopy and chromatography analysis were used for identification of compounds present in ChloF. RESULTS AND DISCUSSION: After the fractionation, the ChloF 70mg/kg was the most active fraction, reducing the immobility time by 22%. Pre-treatments with both PCPA and AMPT abolished the ChloF effects, suggesting that ChloF antidepressant-like effect is dependent on serotonergic and catecholaminergic systems. ChloF did not inhibited MAO-A or MAO-B activity, excluding this as possible mechanism of action. ChloF augmented hippocampal BDNF level, which could be accounted for its antidepressant-like effect. Phytochemical screening showed the presence of saponins, tannins, steroids and triterpene in the PEx, and the presence of triterpene and steroids in ChloF. The spectroscopy and chromatography analysis identified lupeol, ß-sitosterol and stigmasterol in ChloF. CONCLUSION: ChloF is the fraction that better retained the crude extract active constituents. ChloF presents antidepressant-like effect that involves both serotonergic and catecholaminergic systems without inhibiting MAO enzymatic activity; this fraction also increases the hippocampal BDNF levels.

Involvement of GABAergic pathway in the sedative activity of apigenin, the main flavonoid from Passiflora quadrangularis pericarp

Abstract In the current study we showed that oral administration of an aqueous extract of Passiflora quadrangularis L., Passifloraceae, pericarp results in a significant prolongation of the sleep duration in mice evaluated in the ethyl ether-induced hypnosis test which indicates sedative effects. Apigenin, the main flavonoid of the extract, induced a similar sedative response when applied alone, at a dose equivalent to that found in the extract, suggesting that apigenin is mediating the sedative effects of P. quadrangularis extract. In addition, the sedative effect of apigenin was blocked by pretreatment with the benzodiazepine antagonist flumazenil (1 mg/kg), suggesting an interaction of apigenin with gamma-aminobutyric acid type A (GABAA) receptors. However, apigenin at concentrations 0.1–50 µM failed to enhance GABA-induced currents through GABAA receptors (α1β2γ2S) expressed in Xenopus oocytes. Nevertheless, based on our results, we suggest that the in vivo sedative effect of the P. quadrangularis extract and its main flavonoid apigenin maybe be due to an enhancement of the GABAergic system.