RESUMEN
Annona muricata Linnaeus (Annonaceae), popularly known as graviola, is used in folk medicine as both sedative and anticonvulsant. This study correlates the neurochemical profile with the behavioral effects of the hydroalcoholic extract from the leaves of Annona muricata (HLEAM) in mice, proposing to elucidate their mechanism of action on the central nervous system. Flavonoids and phenolic compounds were identified and quantified by High Performance Liquid Chromatography (HPLC) method. The acute toxicity (median lethal dose - LD50) was determined by probitos method using the percentage of mortality based on the Hippocratic screen. HLEAM (25, 50 and 100 mg/kg) was tested, intraperitoneally (i.p.), in models of sedation, anxiety, motor coordination, and seizures. The endogenous levels of dopamine, norepinephrine and DOPAC were assayed by reverse-phase HPLC with electrochemical detection. The HPLC analysis of the extract revealed the presence of flavonoids (quercetin, isoquercitrin, quercitrin, rutin, and kaempferol) and phenolics acids (gallic, chlorogenic, ellagic and caffeic acids). The LD50 was 1091.7 mg/kg and Hippocratic screening indicated central nervous system depressant effect. HLEAM presented sedative effects at doses of 25, 50, and 100 mg/kg, as well as anxiolytic and anticonvulsant effects at a dose of 100 mg/kg. In addition, these effects were partially reversed by flumazenil. The monoamines analysis by HPLC showed that HLEAM decreased the level of norepinefrine and dopamine in the mouse brain striatum. Thus, the results indicate a possible interaction of HLEAM with the GABAergic and monoaminergic systems, adding medicinal value to the popular use of the plant for the treatment of behavioral and neurological disorders.
RESUMEN
This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α2-adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers.