Afrormosin, an Isoflavonoid from Amburana cearensis A. C. Smith, Modulates the Inflammatory Response of Stimulated Human Neutrophils.

Isoflavones are phytoestrogens known by their anti-inflammatory, antioxidant and immunomodulatory properties. Presently, there is no information on whether afrormosin, an isoflavone from Amburana cearensis A.C. Smith (Fabaceae), has some effect on the inflammatory response from stimulated human neutrophils. Thus, the aim of this study was to evaluate the anti-inflammatory and antioxidant potentials of afrormosin on human neutrophils. Neutrophils (2.5 × 10(6) cells/mL) were incubated with afrormosin (3.35-335.2 µM) prepared from a product isolated from Amburana cearensis A.C. Smith with a 78.5% degree of purity and stimulated by the addition of cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate-13-acetate (PMA). Afrormosin inhibited the neutrophil degranulation induced by fMLP (10.47-335.2 µM) or PMA (0.33-167.6 µM), myeloperoxidase activity (3.3-335.2 µM), TNF-α secretion (16.7-335.2 µM) and the reactive oxygen species (ROS) generation (16.7-335.2 µM). On the other hand, afrormosin did not show any effect either on elastase or as a free radical scavenger. These data suggest that afrormosin modulates intermediary steps of the neutrophil ROS generation process. In addition, the modulatory effect of afrormosin on human neutrophil degranulation seems to be directed towards PMA-induced activation, indicating a potent inhibition of the protein kinase C activity. This study provided evidence, for the first time, to support the anti-inflammatory and antioxidant activities of afrormosin, creating novel insights into the pharmacological actions of this natural isoflavone.

Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice.

In the present work, we studied the effects of piplartine (PIP), an amide alkaloid isolated from the roots of Piper tuberculatum (Piperaceae), in the elevated plus maze, open field, rota rod, pentylenetetrazole (PTZ)-induced seizures, and forced swimming tests, in mice (Swiss, male, 25 g) to assess anxiolytic, sedative, muscle relaxant, anticonvulsant and antidepressant effects, respectively. Results showed that PIP (50 and 100 mg/kg, i.p.), similarly to diazepam, significantly increased not only the number of entrances (100% and 66%, respectively) but also the time of permanence in the open arms (104% and 199%, respectively), indicating that PIP presents an anxiolytic activity. Both effects were completely blocked by the previous administration of flumazenil what suggests the involvement of benzodiazepine type receptors. In the open field test, although PIP did not alter the number of crossings, it significantly increased grooming (103% and 119%) and rearing (60% and 23%), at the doses of 50 and 100 mg/kg respectively, as compared to controls. However, in the rota rod test, PIP was devoid of effect. Although in the PTZ-induced convulsion test, PIP did not alter the latency time for the onset of the first convulsion, as compared to controls, it significantly reduced in 58% and 60%, respectively, the animal's latency time to death. Furthermore, a significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after PIP administration (41% and 75% decrease, at the doses of 50 and 100 mg/kg, respectively), suggesting an antidepressant effect, similarly to that observed with imipramine, a classical antidepressant drug used as standard. In conclusion, we showed that PIP presents significant anxiolytic and antidepressant activities, making this drug potentially useful in anxiety and depression.

Analgesic and anti-inflammatory activities of the isomeric mixture of alpha- and beta-amyrin from Protium heptaphyllum (Aubl.) march.

In the present work, we demonstrated that the mixture of alpha- and beta-amyrin (AMI) from Protium heptaphyllum has antinociceptive activity as was evident from the writhing and formalin tests in mice. AMI (10 and 50 mg/kg, i.p.) inhibited writhing in 73 and 94%, respectively, while preferentially inhibiting the 2nd phase of the response (37 and 51; and 60 and 73% inhibitions of the 1st and 2nd phases, respectively) to the formalin test. Naloxone, an opioid antagonist, did not reverse the antinociceptive effect. AMI (50 mg/kg, i.p.) was also active in the hot plate test, increasing the reaction time to thermal stimulus after 30 and 60 min, by 62 and 71%, respectively. A preventive antiedematogenic effect was observed in mice that had a carrageenan-induced paw edema. Paw volume was significantly and dose-dependently decreased by 39, 42 and 53%, three hours after administration of 10, 25 and 50 mg/kg doses, i.p., respectively. AMI (25 and 50 mg/kg, i.p.) was also able to reverse the edema already induced by carrageenan (curative effect). AMI (10 and 25 mg/kg, i.p.) was equally effective in the dextran- induced paw edema (preventive effect), reducing the paw volume by 50 and 60% at the 2nd hour, and by 63 and 73% at the third hour post-dose. AMI (50 mg/kg, i.p.) reverted the edema already formed after the dextran injection (curative effect). In conclusion, AMI demonstrated peripheral and central analgesic effects independent of the opioid system, and also showed a potent anti-inflammatory activity. The antiinflammatory activity was potentiated by both indomethacin and thalidomide, suggesting a potential involvement of prostaglandins and TNFalpha inhibitions.

Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced neurotoxicity.

The present work studied in vivo neuroprotective effects of n-acetylserotonin (NAS), the immediate precursor of melatonin, on the dopaminergic system, in rats lesioned with the unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Two weeks after the lesion, the dopamine receptor agonist, apomorphine, produced rotational asymmetry, and the NAS treatment significantly reduced the motor deficit following the apomorphine challenge. The apomorphine-induced rotational behavior was blocked by 84, 86 and 53% after NAS, at doses of 2, 5 and 10 mg/kg, i.p., respectively. The injection of 6-OHDA significantly decreased DA, DOPAC and HVA levels in the rat striatum. In contrast, the NAS (2, 5 and 10 mg/kg, i.p., daily for 7 days) treatment partially reversed the decreases caused by 6-OHDA, and the neurotransmitter levels were brought to approximately 50% of that observed in the contralateral sides. NAS was more efficient at the smaller doses. NAS (5 mg/kg) produced an up-regulation of D1 (37%) and D2 (37%) receptors associated with a decrease in Kd values.