Evaluation of the antinociceptive effect generated by citronellal monoterpene isomers.

Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.

Sensitivity of hyperparasitic fungi to alternative products for use in the control of papaya black spot / Sensibilidade de fungos hiperparasitas a produtos alternativos para uso no controle da pinta preta do mamoeiro

Abstract The use of more than one control technique can maximize the reduction of the damages caused by the fungus Asperisporium caricae causal agent of the black spot in the papaya crop. The objective of this work was to evaluate the sensitivity of the fungi Hansfordia pulvinata and Acremonium spp. to alternative products with potential for use in the control of the black-spotted ptarmigan. Three isolates of Acremonium spp. (A-598, A-602 and A-617) and an isolate of H. pulvinata (H-611) were grown in BDA medium containing Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separately. The Amistar 500WG ® fungicide was used as a positive control and pure BDA as a negative control. The toxicity of the tested products was determined based on the values of the biological index, derived from the means of mycelial growth, sporulation and germination of conidia, in each experimental unit. In this way it was possible to select the products classified as compatible for all isolates, and to test them in vivo. In the greenhouse, only the isolates and isolates with selected products, were applied in papaya plants with foliar symptoms of black-spotted. The incidence of leaves with hyperparasites and the percentage of black-painted lesions colonized by the tested isolates were evaluated. Thus, the H-611 isolate proved to be compatible with most of the alternative products tested, except with Hortifos®. Bion® and Matrix® products were compatible with all tested isolates and could be used in conjunction with Acremonium spp. and H. pulvinata to control the papaya black spot, since these products did not present toxicity on the hyperparasitic fungi.

Resumo O uso de mais de uma técnica de controle pode maximizar a redução dos danos causados pelo fungo Asperisporium caricae agente causal da pinta preta na cultura do mamoeiro. O objetivo deste trabalho foi avaliar a sensibilidade dos fungos Hansfordia pulvinata e Acremonium spp. a produtos alternativos com potencial para uso no controle da pinta-preta. Três isolados de Acremonium spp. (A-598, A-602 e A-617) e um isolado de H. pulvinata (H-611) foram cultivados em meio BDA contendo Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separadamente. Fungicida Amistar 500WG® foi utilizado como controle positivo e BDA puro, como controle negativo. A toxicidade dos produtos testados foi determinada com base nos valores do índice biológico, provenientes das médias do crescimento micelial, esporulação e germinação de conídios, em cada unidade experimental. Dessa forma foi possível selecionar os produtos classificados como compatíveis para todos os isolados, e testá-los in vivo. Em casa de vegetação, somente os isolados e os isolados com produtos selecionados, foram aplicados em plantas de mamoeiro com sintomas foliares de pinta-preta. Avaliaram-se a incidência de folhas com hiperparasitas e a porcentagem de lesões de pinta-preta colonizadas pelos isolados testados. Assim o isolado H-611 mostrou-se compatível com a maioria dos produtos alternativos testados, exceto com Hortifos®. Os produtos Bion® e Matriz® apresentaram compatibilidade com todos os isolados testados, podendo ser utilizados em conjunto com o Acremonium spp. e H. pulvinata para controlar a pinta-preta do mamoeiro, uma vez que estes produtos não apresentaram toxidade sobre os fungos hiperparasitas.

Sensitivity of hyperparasitic fungi to alternative products for use in the control of papaya black spot.

The use of more than one control technique can maximize the reduction of the damages caused by the fungus Asperisporium caricae causal agent of the black spot in the papaya crop. The objective of this work was to evaluate the sensitivity of the fungi Hansfordia pulvinata and Acremonium spp. to alternative products with potential for use in the control of the black-spotted ptarmigan. Three isolates of Acremonium spp. (A-598, A-602 and A-617) and an isolate of H. pulvinata (H-611) were grown in BDA medium containing Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separately. The Amistar 500WG ® fungicide was used as a positive control and pure BDA as a negative control. The toxicity of the tested products was determined based on the values of the biological index, derived from the means of mycelial growth, sporulation and germination of conidia, in each experimental unit. In this way it was possible to select the products classified as compatible for all isolates, and to test them in vivo. In the greenhouse, only the isolates and isolates with selected products, were applied in papaya plants with foliar symptoms of black-spotted. The incidence of leaves with hyperparasites and the percentage of black-painted lesions colonized by the tested isolates were evaluated. Thus, the H-611 isolate proved to be compatible with most of the alternative products tested, except with Hortifos®. Bion® and Matrix® products were compatible with all tested isolates and could be used in conjunction with Acremonium spp. and H. pulvinata to control the papaya black spot, since these products did not present toxicity on the hyperparasitic fungi.

Orofacial antinociceptive activity of (S)-(-)-perillyl alcohol in mice: a randomized, controlled and triple-blind study.

This study investigated the antinociceptive effects of (S)-(-)-perillyl alcohol (PA) on orofacial nociception in Swiss male mice using formalin-, capsaicin-, and glutamate-induced pain tests. For each test, eight animals per group were pre-treated intraperitoneally by a blinded investigator with PA (50 or 75mg/kg), morphine, or vehicle (saline+0.2% Tween 80). The treatment was performed before the induction of orofacial nociception by injecting formalin, capsaicin, or glutamate solution into the right area of the upper lip. The orofacial nociceptive behaviour was timed in all tests by an investigator who was blinded to the treatments. The statistical analysis was performed using confidence intervals (CI), the effect size, and power. PA blocked the orofacial nociceptive behaviour at both doses tested (P<0.05) similarly to morphine (P>0.05), in all tests. The effect size was high in the phase 1 formalin test for 50mg/kg PA (95% CI 0.48-2.31, power 84.6%) and 75mg/kg PA (95% CI 0.82-2.76, power 96.2%), in phase 2 for 75mg/kg PA (95% CI 0.44-2.26, power 82.3%), and in the glutamate test for 75mg/kg PA (95% CI 1.11-3.16, power 99.2%). These findings show strong evidence for the antinociceptive properties of PA in the orofacial region.

Sensitivity of hyperparasitic fungi to alternative products for use in the control of papaya black spot

Abstract The use of more than one control technique can maximize the reduction of the damages caused by the fungus Asperisporium caricae causal agent of the black spot in the papaya crop. The objective of this work was to evaluate the sensitivity of the fungi Hansfordia pulvinata and Acremonium spp. to alternative products with potential for use in the control of the black-spotted ptarmigan. Three isolates of Acremonium spp. (A-598, A-602 and A-617) and an isolate of H. pulvinata (H-611) were grown in BDA medium containing Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separately. The Amistar 500WG ® fungicide was used as a positive control and pure BDA as a negative control. The toxicity of the tested products was determined based on the values of the biological index, derived from the means of mycelial growth, sporulation and germination of conidia, in each experimental unit. In this way it was possible to select the products classified as compatible for all isolates, and to test them in vivo. In the greenhouse, only the isolates and isolates with selected products, were applied in papaya plants with foliar symptoms of black-spotted. The incidence of leaves with hyperparasites and the percentage of black-painted lesions colonized by the tested isolates were evaluated. Thus, the H-611 isolate proved to be compatible with most of the alternative products tested, except with Hortifos®. Bion® and Matrix® products were compatible with all tested isolates and could be used in conjunction with Acremonium spp. and H. pulvinata to control the papaya black spot, since these products did not present toxicity on the hyperparasitic fungi.

Resumo O uso de mais de uma técnica de controle pode maximizar a redução dos danos causados pelo fungo Asperisporium caricae agente causal da pinta preta na cultura do mamoeiro. O objetivo deste trabalho foi avaliar a sensibilidade dos fungos Hansfordia pulvinata e Acremonium spp. a produtos alternativos com potencial para uso no controle da pinta-preta. Três isolados de Acremonium spp. (A-598, A-602 e A-617) e um isolado de H. pulvinata (H-611) foram cultivados em meio BDA contendo Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separadamente. Fungicida Amistar 500WG® foi utilizado como controle positivo e BDA puro, como controle negativo. A toxicidade dos produtos testados foi determinada com base nos valores do índice biológico, provenientes das médias do crescimento micelial, esporulação e germinação de conídios, em cada unidade experimental. Dessa forma foi possível selecionar os produtos classificados como compatíveis para todos os isolados, e testá-los in vivo. Em casa de vegetação, somente os isolados e os isolados com produtos selecionados, foram aplicados em plantas de mamoeiro com sintomas foliares de pinta-preta. Avaliaram-se a incidência de folhas com hiperparasitas e a porcentagem de lesões de pinta-preta colonizadas pelos isolados testados. Assim o isolado H-611 mostrou-se compatível com a maioria dos produtos alternativos testados, exceto com Hortifos®. Os produtos Bion® e Matriz® apresentaram compatibilidade com todos os isolados testados, podendo ser utilizados em conjunto com o Acremonium spp. e H. pulvinata para controlar a pinta-preta do mamoeiro, uma vez que estes produtos não apresentaram toxidade sobre os fungos hiperparasitas.

CNS pharmacological effects of the hydroalcoholic extract of Sida cordifolia L. leaves.

Sida cordifolia L. (Malvaceae), known as "malva branca", is a plant used in the popular medicine for the treatment stomatits, of asthma and nasal congestion. This work researched the acute toxicity of Sida cordifolia and its action on the central nervous system (CNS) because no data in the literature have been found about of pharmacological activity of this plant in the CNS. The hydroalcoholic extract of Sida cordifolia leaves (HESc) was used and the psychopharmacology approach began with the determination of LD(50), where a low toxicity was observed in mice. Depressive activity on CNS was demonstrated by several alterations in mice's behavior in the pharmacological screening. In the motility test, the HESc showed significant reduction of spontaneous activity at a dose of 1000 mg/kg (i.p.) at 30 and 60 min. The same form the HESc also decreased the ambulation and rearing in open-field test at 30, 60 and 120 min at a dose of 1000 mg/kg (i.p.).

Anorectic and behavioural effects of chronic Cissampelos sympodialis treatment in female and male rats.

Male and female rats were treated daily for 13 weeks with an ethanol extract of Cissampelos sympodialis leaves (9, 45 and 225 mg[sol ]kg). The food consumption, body weight and behavioural effects in the open-field test were evaluated by weekly monitoring. The results showed that the extract chronic treatment in female rats (45 and 225 mg[sol ]kg) reduced significantly the food intake and the body weight, and produced several alterations in the open-field test. These findings indicate that repeated oral administration of the extract may produce a sex-dependent difference in anoretic and behavioural effects.

Antiparkinsonian-like effects of Plumbago scandens on tremorine-induced tremors methodology.

Tremorine-induced tremors model is used to evaluate antiparkinsonian drugs because rest tremor is a sign that distinguishes Parkinson's disease (PD) from other diseases. The effects of crude ethanolic extract (CEE) and total acetate fraction (TAF) of Plumbago scandens were investigated at several doses. These extracts at doses of 125 and 250 mg/kg i.p. failed to reduce tremors in tremorine-treated mice. TAF showed significant effects only at a dose of 500 mg/kg. Both CEE and TAF at doses of 1000 and 2000 mg/kg i.p. suppressed the tremors in a dose-dependent fashion for 60 min. Biperiden, an anticholinergic drug, was used as standard at a dose of 3 mg/kg i.p. This study suggests that P. scandens is a plant with possible therapeutic value for PD.

Central antinociceptive effect of a hydroalcoholic extract of Dioclea grandiflora seeds in rodents.

The acute treatment of rats and mice with a hydroalcoholic extract from the seeds of Dioclea grandiflora (EHDg) at doses of 250 and 500 mg/kg, by intraperitoneal or oral administration, produced a significant antinociceptive effect in the tail flick and hot plate tests, an effect which was inhibited by naloxone. EHDg given to mice daily for 30 days at a dose of 500 mg/kg, did not cause any observable toxic effect nor any alteration in the pattern of antinociceptive response by the tail immersion test during the course of this treatment. These results suggest that EHDg has a central antinociceptive action devoid of tolerance effect typical of opioid drugs.

Plants with central analgesic activity.

The present communication constitutes a global review on plant analgesic activity with special emphasis on those found in different parts of the world, including Brazil, which act on the central nervous system. One hundred and sixty six plants belonging to 79 families are reported.

Anticonvulsant properties of N-salicyloyltryptamine in mice.

A new tryptamine analogue, N-salicyloyltryptamine (STP), a potential central nervous system (CNS) depressant, was tested in the pentylenetetrazol (PTZ) and maximal electroshock (MES) models of epilepsy in mice. When administered concurrently, STP (100 mg/kg ip) significantly reduced the number of animals that exhibited PTZ-induced seizures and eliminated the extensor reflex of maximal electric-induced seizures test in 50% of the experimental animals. In addition, it showed protection in the PTZ test by diminishing the death rate.

CNS pharmacological effects of the total alkaloidal fraction from Albizia inopinata leaves.

The total alkaloidal fraction of Albizia inopinata leaves (FLA) was investigated for its central nervous system (CNS) effects. FLA (10 mg/kg, i.p.) significantly reduced (45%) the locomotor activity in mice. In addition, it inhibited the conditioned avoidance response behavior and induced ptosis in rats. On the other hand, FLA did not exert significant effect on catalepsy, but potentiated the haloperidol-induced catalepsy. No effect was observed on sleep induced by sodium pentobarbital or apomorphine-induced stereotypes.

Endothelium-derived nitric oxide is involved in the hypotensive and vasorelaxant responses induced by the aqueous fraction of the ethanolic extract of the leaves of Albizia inopinata (Harms) G. P. Lewis in rats.

The acute cardiovascular effects of an aqueous fraction of the ethanolic extract of the leaves (AFL) of Albizia inopinata (Harms) G. P. Lewis (Leguminosae) were studied in rats using a combined in vivo and in vitro approach. In conscious, unrestrained rats, AFL (5, 10 and 20 mg/kg(-1) body wt. i.v., randomly) produced a significant and dose-dependent hypotension associated with increases in heart rate and cardiac output, and with a strong reduction in total peripheral resistances. The hypotensive response to AFL (20 mg/kg(-1) body wt.) was attenuated significantly after nitric oxide (NO) synthase blockade (L-NAME, 20 mg/kg(-1) body wt. i.v.). Furthermore, under these conditions, the associated tachycardia was inhibited completely. In isolated rat aortic rings, increasing concentrations of AFL (10, 20, 40 and 80 microg/ml(-1)) were able to antagonize the effects of phenylephrine- (1 microM) and KCl- (80 mM) induced contractions (IC50 value 65 +/- 4 and 54 +/- 6 microg/ml(-1), respectively). The smooth muscle-relaxant activity of AFL was inhibited similarly either removal of the vascular endothelium or by L-NAME (10 and 100 microM), but was not affected significantly by atropine (1 microM) or indomethacin (10 microM). In isolated rat atrial preparations, AFL (30, 100, 300 and 500 microg/ml(-1)) produced concentration-related negative inotropic and chronotropic effects (IC50 value = 274 +/- 53 and 335 +/- 23 microg/ml(-1), respectively). These results suggest that in rats, the hypotensive effect of AFL is due to a peripheral vasodilation, at least partly secondary to the release of NO by the vascular endothelium. The direct cardio-depressant actions of AFL are of little importance in the systemic effects of the extract.

Neuronal vacuolation of the trigeminal nuclei in goats caused by ingestion of Prosopis juliflora pods (mesquite beans).

Three groups of 6 goats each were fed a ration containing 30, 60, or 90%, on a dry matter base, of Prosopis juliflora pods. A control group of 4 goats ingested only the basic ration. Two hundred and ten days after the start of the experiment 3 goats that ingested 60% pods in and 4 that ingested 90% had mandibular tremors, mainly during chewing. All animals were killed after 270 d of ingestion. No gross lesions were observed. Histologic lesions were characterized by fine vacuolation of the pericaryon of neurons from the trigeminal nuclei. Occasionally neurons of the oculomotor nuclei were also affected. Wallerian degeneration was occasionally observed in the mandibular and trigeminal nerves. Denervation atrophy of the masseter, temporal, hypoglossus, genioglossus, styloglossus, medial pterygoid and lateral pterygoid muscles was seen. The clinical signs from feeding the P juliflora pods were caused by a selective toxicity to neurons of some cranial nerve nuclei.

Endothelium-independent vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora, in the rat aorta.

We have investigated the endothelium-independent vasorelaxant effect of the new flavonoid dioclein (5,2',5'-trihydroxy-6-7-dimethoxyflavanone) in the rat aorta. In endothelium-denuded vessels, dioclein induced a concentration-dependent relaxation of aortic rings precontracted with noradrenaline (IC50 = 3.5+/-0.89 x 10(-4) M and KCl (IC50 = 5.2+/-1.2 x 10(-4) M). In the absence of extracellular calcium, dioclein reduced the contraction induced by noradrenaline (maximal reduction approximately 33%) but not that induced by caffeine. Dioclein also produced a concentration-dependent inhibition of the sustained contractions induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in normal (IC50 = 4.0+/-0.2 x 10(-4) M) and Ca2+-free solution (IC50 = 4.0+/-0.3 x 10(-4) M). The results indicate that the endothelium-independent vasorelaxant effect of dioclein may be explained by inhibition of contractions dependent on activation of protein kinase C, voltage-dependent Ca2+ influx and on the release of intracellular Ca2+ stores sensitive to noradrenaline.

Isolamento biomonitorado de alcalóides tóxicos de Prosopis juliflora (algaroba) / Bioassay-guided isolation of toxic alkaloids of Prosopis juliflora (mesquite)

Uma investigação fitoquímica das vagens de Prosopis juliflora cultivada na região semi-árida do Estado da Paraíba e monitorada através de testes farmacológicos levou ao isolamento, purificação e identificação do alcalóide principal juliprosopina. A presença de outros constituintes químicos em mistura, tais como juliprosina e juliprosineno, foi verificada na fração dos alcalóides totais através de uma análise do espectro de RMN de 13C. Este trabalho sugere que a toxicidade, observada em animais de laboratório, está quimicamente relacionada com os alcalóides piperidínicos presentes nas vagens desta leguminosa.

A phytochemical investigation of the pods of Prosopis juliflora cultivated in the semi arid region of the State of Paraiba, monitored by pharmacological tests, led to the isolation, purification and identification of its main alkaloid - juliprosopine. The presence of other compounds such as juliprosine and juliprosinene, was observed through analysis of 13C NMR. This work suggests that the toxic activity, observed in laboratory animals, is chemicaly related with the piperidine alkaloids present in the pods of this Leguminosae.

Central depressant effects of reticuline extracted from Ocotea duckei in rats and mice.

Neuropharmacological studies were carried out with reticuline, a benzylisoquinoline alkaloid, isolated from Ocotea duckei Vattimo. It was found that reticuline (50-100 mg/kg i.p.) produced alteration of behaviour pattern, prolongation of pentobarbital-induced sleep, reduction in motor coordination and D-amphetamine-induced hypermotility and suppression of the conditioned avoidance response. These observations suggest that reticuline possesses potent central nervous system depressant action.

Antidepressant effect of an ethanolic extract of the leaves of Cissampelos sympodialis in rats and mice.

An ethanolic extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) was found to potentiate the toxicity of pentylenetetrazol in mice. Similar to imipramine, the extract also reduced the immobility period in the forced swimming test in mice and reversed the degree of ptosis and catalepsy induced by reserpine in rats. These results suggest that the extract possesses antidepressant activity and the reported phosphodiesterase inhibitory activity of the plant may account for the observed antidepressant effect.

Cardiovascular effects of an aqueous fraction of the ethanol extract of the leaves of Cissampelos Eichl. in the rat.

The cardiovascular effects of the aqueous fraction of the ethanol extract of the leaves (AFL) of Cissampelos sympodialis Eichl. were evaluated in this work. In conscious freely moving rats, AFL (0.5, 1, 2, 4 and 8 mg/kg, i.v.) increased the mean arterial pressure (MAP) by 7 ± 2,16 ± 5, 33 ± 5, 43 ± 3 and 38 ± 4 mmHg, respectively, followed by a significant decrease in heart rate. After cardiac autonomic blockade (atenolol + atropine, 2 mg/kg, i.v., each), the hypertensive effects produced by AFL (2 and 4 mg/kg) were potentiated. However, AFL was ineffective in producing bradycardia. In anesthetized rats, AFL (4 mg/kg) induced similar increases in MAP (34 ± 4 mmHg) and bradycardia (-160 ± 24 bpm). Further, it induced a third-degree atrioventricular (AV) blockade. Nevertheless, both bradycardia and AV-blockade were completely abolished after atropine. While the AFL failed to induce bradycardia directly in the isolated perfused rat heart, in isolated right and left rat atria, it produced positive chronotropic and inotropic effects. The results demonstrate that the AFL markedly increases blood pressure in conscious unrestrained and anesthetized rats and improves heart rate and contractility in isolated perfused atrial preparations. Furthermore, the results suggest that the bradycardia associated with increase in blood pressure is reflex in origin.

Analgesic effect of Dioclea grandiflora constituents in rodents.

An aqueous fraction and dioclein (5,2',5'-trihydroxy-6,7-dimethoxyflavanone) obtained from the ethanolic extract of the Dioclea grandiflora were tested for their analgesic effect in mice and rats employing acetic-induced writhing and tail flick tests, respectively. When administered intraperitoneally the two agents exhibited significant analgesic effects. The activity of both dioclein and aqueous fraction apparently involves an opiate-like mechanism, since their analgesic action was attenuated by naloxone pretreatment.