Evaluation of Gastroprotective Activity of Linoleic Acid on Gastric Ulcer in a Mice Model.

BACKGROUND: Gastric ulcer has been a major cause of morbidity and mortality worldwide, and it has been linked to factors such as nutritional deficiency, smoking, stress, and continuous intake of non-steroidal antiinflammatory drugs (NSAIDs). The search for new anti-ulcer therapeutic agents has been the subject of several studies. Recently, the gastroprotective effect of Celtis iguanaea has been reported, with linoleic acid (LA) responsible for many of the therapeutic effects of this medicinal plant. AIMS: This study aims to investigate the gastroprotective activity and the possible mechanisms in which LA may be involved through different experimental assays in mice. METHODS: The gastroprotective activity of LA was evaluated in the ulcer induced by indomethacin, HCl/EtOH, hypothermic-restraint stress and pyloric ligation. For the investigation of gastroprotective mechanisms, the quantification of the volume (mL), pH and total acidity of gastric secretion were considered. RESULTS: The oral administrations of 25 mg/kg, 50 mg/kg or 100 mg/kg of body weight of LA were capable of protecting the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and oral/intraduodenal treatment administrations of 50 mg/kg LA showed protection from ulcers induced by indomethacin, hypothermic-restraint stress and pyloric ligation. CONCLUSION: The results of this study show the gastroprotective role of LA in gastric mucosal damage induced by all assayed distresses. The observed gastroprotection possibly occurs due to the mediated increase of mucosal defensive factors.

A new piperazine derivative: 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one with antioxidant and central activity.

In the scope of a research program aimed at developing new drugs for the treatment of central nervous system diseases, we describe herein the synthesis and pharmacological evaluation of 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one (LQFM180). This compound showed antioxidant activity in two models, electroanalytical assays, and DPPH activity. Moreover, in behavioral tests as the open field test LQFM180 (9.4, 18.8, and 37.6 mg/kg, per oral (p.o.)), we detected anxiolytic-like activity. In the sodium pentobarbital-induced sleep test, LQFM180, in all doses, decreased the latency to sleep and increased sleep duration, indicating central depressant activity; moreover, in the chimney test, LQFM180 did not alter motor activity. LQFM180 (18.8 mg/kg, p.o.) increased the time and number of entries on open arms in the elevated plus maze test, suggesting anxiolytic-like activity, which was reversed by NAN-190 and p-chlorophenylalanine, indicating a role of the serotonergic pathway on this effect. In the forced swimming test, LFQM180 (18.8 mg/kg, p.o.) decreased immobility time, suggesting antidepressant-like activity, which was reversed by monoaminergic antagonists, indicating a role for the serotonergic, noradrenergic, and dopaminergic pathways. Competition binding assays showed that LQFM180 was able to bind to the α1B, 5-HT1A, and D2 receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.