Alyne Mara Rodrigues de Carvalho

(−)-α-Bisabolol-induced gastroprotection is associated with reduction in lipid peroxidation, superoxide dismutase activity and neutrophil migration

This work examined the gastroprotection of (-)-α-bisabolol, an unsaturated optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants. (-)-α-Bisabolol has been described as a compound capable of reducing the gastric ulcer area in response to absolute ethanol. We evaluated the gastroprotection of (-)-α-bisabolol in ethanol-induced gastric lesions model through histopathological assessment, measurement of the membrane lipids peroxidation (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and the nitrite amount. Our results showed that (-)-α-bisabolol was able to reduce injuries associated with the administration of ethanol and the formation of thiobarbituric acid reactive substances (MDA) was also able to increase SOD activity and reduce the influx of cells inflammatory (neutrophils) in the gastric mucosa. The effect of (-)-α-bisabolol seems to be unrelated to the nitric oxide. (-)-α-Bisabolol caused a reduction of catalase activity. These findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol.

Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action.

The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K+ channels (KATP channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-l-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, KATP channel opening, and antioxidant properties.

Bioactivity and potential therapeutic benefits of some medicinal plants from the Caatinga (semi-arid) vegetation of Northeast Brazil: a review of the literature

Medicinal plants have been used in traditional medicine for several thousand years all over the world. In this sense, information from Brazilian ethnic groups on folk medicine have contributed to the discovery of pharmacological activities from various plant-derived agents potentially leading to the innovative drugs. The Caatinga (semi-arid) vegetation is a highly threatened biome, covering a vast area in northeastern Brazil and has suffered from strong human influence for many decades. Many plants species found in the Caatinga have been widely used in folk medicine and for commercial manufacturing of phytotherapeutic products. Thus, the present review aims to disseminate to the scientific community some known species of medicinal plants found in the Caatinga that have been studied and analyzed in pharmacological scientific assays. Among the species that stood out for their local importance and multiplicity of uses were: Amburana cearensis (umburana-de-cheiro), Anadenanthera colubrina (Vell.) Brenan (angico-branco), Anacardium occidentalis L. (cajueiro), Bauhinia forficata Link (mororo), Cissus sicyoides L. (insulina-vegetal), Myracrodruon urundeuva Allemao (aroeira-do-sertao) and Zingiber officinalis L. (gengibre). The present study shows that several herbal constituents from Caatinga plants, whose pharmacological actions have been well characterized, may be relevant candidates for future and innovative therapeutic development.

TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate

BACKGROUND Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT. METHODS The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists. RESULTS CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CATs antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT. CONCLUSION The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CATs antinociceptive mechanism.

Evaluation of the anti-inflammatory activity of riparin II (O-methil- N-2-hidroxi-benzoyl tyramine) in animal models

Riparin II (RipII), an alkamide isolated from the green fruit of Aniba riparia, was tested in the various animal models of inflammation to investigate its anti-inflammatory activity. Male Wistar rats (180-240g) were treated with RipII by gavage at doses 25 or 50mg/kg, before initiating the inflammatory responses. The tests used were paw edema induced by carrageenan, dextran, histamine or serotonin; peritonitis induced by carrageenan and fMLP, as well as the measurement of MPO activity, TNF-α and Il-1β amount in the peritoneal fluid. In the animal models of carrageenan and dextran-induced paw edema, the animals treated with RipII showed lower edema than those of the control group. Treatment with RipII also reduced the paw edema induced by histamine but not serotonin. In the carrageenan-induced peritonitis model, treatment with RipII reduced leukocyte migration, the MPO activity and the amount of TNF-α and IL-1β in the peritoneal fluid. In summary, these results indicate that RipII has an anti-inflammatory activity in chemical models of acute inflammation. RipII might be directly or indirectly inhibiting the activity, production or release of pro-inflammatory mediators involved in the generation of the pain associated with inflammation.

Evidence for the involvement of the serotonergic, noradrenergic, and dopaminergic systems in the antidepressant‐like action of riparin III obtained from Aniba riparia (Nees) Mez (Lauraceae) in mice

Previous work has shown that intraperitoneal administration of riparin III (ripIII) reduces immobility time in the forced swimming test (FST), which suggests potential antidepressant activity. As the mechanism of action is not completely understood, this study is aimed at investigating the antidepressant‐like action of ripIII. Following intraperitoneal administration of ripIII at doses of 25 and 50 mg/kg, there were decreases in the immobility time in the FST and tail suspension test without accompanying changes in ambulation (data not shown). The pretreatment of mice with sulpiride (50 mg/kg, i.p.), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and p‐chlorophenylalanine (PCPA, 100 mg/kg, i.p. for, four consecutive days) significantly prevented the anti‐immobility effect of ripIII in the FST. On the other hand, the anti‐immobility effect of ripIII (50 mg/kg, v.o.) was not altered by pretreatment of mice with SCH23390 (15 μg/kg, i.p.) Furthermore, ripIII potentiated the sleeping latency and sleeping time of the pentobarbital‐induced sleeping time test and also potentiated apomorphine (16 mg/kg, i.p.)‐induced hypothermia in mice. In conclusion, the present study provides evidence that the antidepressant‐like effect of ripIII is dependent on its interaction with the serotonergic, noradrenergic (α1‐ and α2‐ receptors), and dopaminergic (dopamine D2 receptors) systems.

Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system

Dehydrodieugenol, known as bis‐eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti‐inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant‐like effect; however, the biological actions of bis‐eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant‐like activity of bis‐eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis‐eugenol was also conducted. Bis‐eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti‐immobility effect of bis‐eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p‐chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2‐adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high‐performance liquid chromatograph revealed significant increase in the 5‐HT, NE and DA levels in brain striatum. The present study indicates that bis‐eugenol possesses antidepressant‐like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function.

Synergistic effect of the L-tryptophan and kynurenic acid with dipyrone or paracetamol in mice.

PURPOSE Our great interest in this work was study the synergism between l-tryptophan and dipyrone or paracetamol as well as the interaction of kynurenic acid (l-tryptophan metabolite) and these analgesics agents utilizing a robust methodology. METHODS We performed the writhing test induced by acetic acid in mice to evaluate the antinociceptive effect of the treatments isolated and combined (p.o. and i.p.). Dose-response curves were constructed and the values of ED50 for treatment alone and combined were statistically compared. In addition, isobolographic analysis was performed and the experimental values were compared with the theoretical values for simple additive effect. RESULTS The combined treatment with l-tryptophan and dipyrone or paracetamol reduced significantly the ED50 of these analgesics when compared to the isolated treatments. l-tryptophan alone has no antinociceptive effect. l-Tryptophan increases the central amount of 5-HT and the synergism with dipyrone is antagonized by the 5-HT depletion. The kyna has an antinociceptive dose-related effect and a synergistic interaction with dipyrone and paracetamol verified by isobolographic analyses and confirmed by experimental values of ED50 of combined treatments were statistically lower than theoretical calculated values for simple additive effect. Melatonin antagonist receptor attenuates the antinociceptive synergism between l-tryptophan and dipyrone. CONCLUSION Our results demonstrate that the increased 5-HT amount on the central nervous system is not per se capable to induce antinociception. The l-tryptophan interacts synergistically with dipyrone and paracetamol both orally and by i.p. route. This effect is dependent on the biotransformation of l-tryptophan to 5-HT and involves kynurenic acid and melatonin receptors.

ANÁLISE DOS RECEITUÁRIOS DE ANTIMICROBIANOS EM UMA FARMÁCIA COMUNITÁRIA DA REDE PRIVADA DE FORTALEZA

Desde o inicio do seculo XX, as doencas infecciosas estao entre as mais importantes causas de mortes. A descoberta de substâncias, capazes de inibir o crescimento ou matar microrganismos, transformou o tratamento das infeccoes. A implantacao de politicas efetivas sobre o uso racional dos antimicrobianos e essencial para melhorar a qualidade na prescricao desses medicamentos e garantir a seguranca da antibioticoterapia. O uso excessivo e incorreto desses medicamentos na clinica humana e veterinaria favorece o aumento da resistencia bacteriana, prejudicando o tratamento das infeccoes causadas por estes agentes, acarretando onus a assistencia a saude, em todo o mundo. Diante das informacoes apresentadas, o uso racional dos antimicrobianos juntamente com seu emprego correto na pratica clinica, se faz necessario, visto que, a incorreta indicacao clinica associada ao nao cumprimento da legislacao dos orgaos reguladores, por parte de profissionais da saude e pacientes, pode acarretar riscos a saude. Objetivo: O presente estudo teve por objetivo analisar os receituarios de antimicrobianos em uma farmacia comunitaria da rede privada de Fortaleza. Tratou-se de um estudo do tipo observacional, descritivo com abordagem quantitativa por meio da analise dos receituarios de antimicrobianos dispensados de maio a setembro de 2017. Foram excluidas prescricoes veterinarias. Analisou-se 842 receituarios, onde nos meses de junho 24,2% e agosto 22,1% ocorreu elevado numero de dispensacao. Houve predominância do sexo feminino 67,7% e a faixa etaria com maior indice foi a de 19-45 anos 44,9%. A maioria dos receituarios estava descritos na forma manuscrita 66,6% e eram oriundos da rede privada 83,1%. Dos receituarios analisados grande parte estava descritos pelo nome fantasia do medicamento 75,5%. A classe do antimicrobiano de maior predominância foi a quinolonas 26,0%. A especialidade do prescritor com maior resultado na dispensacao foi a clinica medica 44,3%. Todos os receituarios dispensados no periodo referente a pesquisa encontravam-se dentro dos parâmetros de legalidade estabelecida pelos orgaos regulamentadores de prescricoes contendo substancias antimicrobianas. Houve um grande numero de dispensacoes nos meses de junho e agosto de 2017, podendo esse numero estar relacionado a doencas sazonais. Com o intuito de melhorar a efetividade da antibioticoterapia e evitar fatores relacionados com o aparecimento da resistencia bacteriana, se faz necessario uma analise mais detalhada quanto ao contexto que envolve criterios de prescricao quanto ao profissional prescritor, para que se utilize o potencial de todas as classes medicamentosas de forma equilibrada. Contudo o uso racional dos antimicrobianos juntamente com seu emprego correto na pratica clinica, se faz necessario, como auxilio as medidas regulatorias da legislacao vigente.

Antinociceptive activity of Riparin II from Aniba riparia : Further elucidation of the possible mechanisms

Riparin II (RipII) has an anti-inflammatory activity potentially due its ability to decrease TNF-α and IL-1β production and its histamine antagonism. The objective of this study was to evaluate the role of RipII in the pain process and the possible antinociceptive mechanisms involved, using classic models of nociception. Male Swiss mice were used in the assays. Determinate the acute toxicity according to the OECD 425 test guideline. The models used were the acetic acid-, formalin-, hot plate and glutamate-induced nociception. For evaluation of antinociceptive effect, the involvement of TRPV1, TRPA1, TRPM8, ASICS, Bradykinin, PKC and PKA were performed using the paw licking using agonists. The acute toxicity study did not detect any clinical signs or changes in behavior or mortality. RipII, administered orally (25 and 50 mg/kg) caused a reduction of nociception induced by acetic acid, formalin (on the second phase) and glutamate. In the investigation of antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 nmol/paw), menthol (1.2 μmol/paw), ASICS (2% acetic acid, pH 1.98) and bradykinin (10 μg/paw). The results showed that TRPV1, TRPA1, TRPM8, ASICS and bradykinin play a role in the antinociceptive effect of RipII. The results also showed that PKA is involved too. These data demonstrate that RipII has a low or not toxicity and produced an important antinociceptive effect through mechanisms that probably involve an interaction, at least in part, TRPV1, TRPA1, TRPM8, ASICS, bradykinin and PKA participate in the RipIIs antinociceptive effect.