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Ethnopharmacological relevance Eugenia brasiliensis Lam. (Myrtaceae) is a Brazilian tree distributed throughout Atlantic rain forest, since Bahia until Santa Catarina state, and is popularly known as “grumixaba, grumixameira, cumbixaba, ibaporoiti, and cereja-brasileira”. The bark and leaves of Eugenia brasiliensis are used in folk medicine as adstringent, diuretic, energizing, anti-rheumatic and anti-inflammatory. This study aimed at investigating the chemical composition, antinociceptive and anti-inflammatory effect of the hydroalcoholic extract of Eugenia brasiliensis (HEEb). Material and methods Chemical composition of the HEEb was determined by High Performance Liquid Chromatography/ESI-Mass Spectrometry (HPLC-ESI-MS/MS). The antinociceptive and anti-inflammatory effects of HEEb (30–300 mg/kg) was verified in mice after oral administration by intra-gastric gavage (i.g.) 60 min prior to experimentation. It was investigated whether HEEb decreases visceral pain and leukocyte migration induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also evaluated whether HEEb decreases nociceptive behavior induced by formalin (including paw edema and temperature), prostaglandin E 2 (PGE 2 ), histamine, and compound 48/80. Finally, we evaluated the effect of HEEb in the chronic inflammatory (mechanical and thermal hypersensitivity) pain induced by complete Freund's adjuvant (CFA), as well as quantifying the concentration of the pro-inflammatory cytokines TNF-α and IL-6 in the paw by ELISA method. Results Seven polyphenols were identified in HEEb by HPLC-ESI-MS/MS analysis. HEEb treatment alleviated nocifensive behavior and leukocyte migration caused by acetic acid. Moreover, HEEb also reduced the inflammatory pain and paw temperature induced by formalin, as well as it decreased nociceptive behavior induced by histamine and compound 48/80. Finally, acute and repeated treatment of animals with HEEb (100 mg/kg, i.g.) markedly reduced the mechanical and thermal (heat) hypersensitivity, besides decrease paw edema and temperature induced by CFA, and this effect was evident until the day 7. Moreover, repeated treatment with HEEb (100 mg/kg, i.g.) significantly reduced the levels of IL-6 and TNF-α in the paw when compared to the CFA group. Conclusions This is the first report showing that HEEb presents antinociceptive and anti-inflammatory effects in the visceral and somatic inflammatory pain in mice, possibly involving the inhibition of histamine receptors and pro-inflammatory cytokines activated pathways. Our results are of interest because they support the use of Eugenia brasiliensis as a potential source of phytomedicine for inflammatory diseases and pain. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant. Aim of the study: To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy. Materials and methods: In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated. Results: The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined with a sub-effective dose of Eugenia brasiliensis decreased the immobility time in the TST. Furthermore, the combined administration of sub-effectives doses of Eugenia brasiliensis with fluoxetine, imipramine and bupropion produced an antidepressant-like effect. Conclusions: This study show, for the first time, the antidepressant-like effect of species of the genus Eugenia, especially Eugenia brasiliensis, whose effects in the TST seem to be mediated by serotoninergic (5-HT1A and 5-HT2 receptors), noradrenergic (α1-adrenoceptor) and dopaminergic (dopamine D 1 and D 2 receptors) systems. [Copyright &y& Elsevier]