We applied a taxonomic approach to select the Eugenia dysenterica (Myrtaceae) leaf extract, known in Brazil as "cagaita," and evaluated its gastroprotective effect. The ability of the extract or carbenoxolone to protect the gastric mucosa from ethanol/HCl-induced lesions was evaluated in mice. The contributions of nitric oxide (NO), endogenous sulfhydryl (SH) groups and alterations in HCl production to the extract's gastroprotective effect were investigated. We also determined the antioxidant activity of the extract and the possible contribution of tannins to the cytoprotective effect. The extract and carbenoxolone protected the gastric mucosa from ethanol/HCl-induced ulcers, and the former also decreased HCl production. The blockage of SH groups but not the inhibition of NO synthesis abolished the gastroprotective action of the extract. Tannins are present in the extract, which was analyzed by matrix assisted laser desorption/ionization (MALDI); the tannins identified by fragmentation pattern (MS/MS) were condensed type-B, coupled up to eleven flavan-3-ol units and were predominantly procyanidin and prodelphinidin units. Partial removal of tannins from the extract abolished the cytoprotective actions of the extract. The extract exhibits free-radical-scavenging activity in vitro, and the extract/FeCl3 sequence stained gastric surface epithelial cells dark-gray. Therefore, E. dysenterica leaf extract has gastroprotective effects that appear to be linked to the inhibition of HCl production, the antioxidant activity and the endogenous SH-containing compounds. These pleiotropic actions appear to be dependent on the condensed tannins contained in the extract, which bind to mucins in the gastric mucosa forming a protective coating against damaging agents. Our study highlights the biopharmaceutical potential of E. dysenterica.

We investigated the psychostimulant, rewarding, and anxiolytic-like effects of pulegone. Possible interactions between pulegone and menthol concerning their psychostimulant effect were also analyzed. General mouse activity after pulegone treatment, and the interacitons between pulegone and menthol, were determined in the open field. The anxiolytic-like activity, motor coordination and strength force were evaluated using the elevated plus maze (EPM), rotarod test and grasping test, respectively. The motivational properties of pulegone were evaluated by pairing the drug effects on the mice with the least preferred compartment (previously determined) of a conditioned place preference (CPP) apparatus. Pulegone increased mouse locomotor activity and immobilization time. Verapamil, but not diltiazem, haloperidol or picrotoxin, decreased the psychostimulation induced by pulegone. Pulegone also decreased grooming and rearing behaviors and caused motor incoordination and weakness at high doses. Pulegone increased the time spent by mice in the open arms of the EPM, and flumazenil pre-treatment did not alter this effect. Pulegone either produced no CPP or induced conditioned place aversion. The changes in mouse ambulatory activity caused by the association of pulegone with menthol were either lower than those predicted by the theoretical curve or not different from the predicted values. Therefore, pulegone induces a verapamil-sensitive psychostimulant effect that appears to independ on the opening of L-type calcium channels. Pulegone has negative reinforcing properties and seems to possess anxiolytic-like actions unrelated to the benzodiazepine site of the γ-aminobutyric acid type A (GABA A ) receptor. Finally, pulegone might act in an addictive or synergic way with menthol.

Mast cell and testosterone interactions involved in renal fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Orchiectomized (ORX) and nonorchiectomized Wistar rats were subjected to UUO, and a nonorchiectomized group was sham-operated (control: SO). Animals from the UUO group were treated with saline or sodium cromoglycate (CG). Some ORX rats from the saline or CG groups also received testosterone propionate replacement (TR). Kidneys and blood were collected 14 d after UUO or SO. Kidney sections were stained with toluidine blue to quantify mast cells, and picrosirius red was used for collagen analysis. Immunohistochemistry for α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) expression was also performed. Plasma testosterone levels (PTLs) were measured. ORX decreased and TR normalized PTLs. UUO increased mast cell density in the kidney pelvis, but not in the kidney parenchyma. UUO increased mast cell degranulation, and CG or ORX inhibited this effect. TR partially reversed the effect of ORX on mast cell degranulation, and CG partially inhibited that effect of TR. UUO increased the collagen areas of the renal parenchyma, whereas CG or ORX abolished that alteration; TR reversed the effects of ORX, and CG partially inhibited that effect of TR. UUO increased tubulointerstitial α-SMA expression and PCNA-positive cells, and these changes were sensitive to ORX or CG to the same degree, while TR again reversed the effect of ORX. Renal fibrosis after UUO appears to be determined by interactions between testosterone and mast cells.