Monoamine Involvement in the Antidepressant-Like Effect of ß-Caryophyllene.

BACKGROUND: Major depressive disorder is a psychiatric disorder that affects 4.4% of the population worldwide. Although the majority of antidepressant drugs ameliorate depressive symptoms, there is still a need for safer and more effective antidepressant. OBJECTIVE: Evaluate the antidepressant-like activity of sesquiterpene compound ß-caryophyllene (BCP) for the possible contribution of the monoamine and hippocampal levels of brain-derived neurotrophic factor (BDNF). METHODS: Male albino Swiss mice were subjected to the forced swimming test after acute treatment and to the tail suspension test after repeated treatment. Hippocampal levels of BDNF were assayed by enzyme-linked immunosorbent assay. RESULTS: The anti-immobility effect of BCP was reverted by pretreatment with an inhibitor of catecholamine synthesis α-methyl-p-tyrosine (100 mg/kg, i.p.), α2-adrenergic antagonist yohimbine (1 mg/kg, i.p.), and ß-adrenergic antagonist propranolol (2 mg/kg, i.p.), but not by pretreatment with either α1-adrenergic antagonist prazosin (1 mg/kg, i.p.) or 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.), thereby suggesting the involvement of α2 and ß-adrenergic receptors, but not of the α1-adrenergic and 5-HT1A serotonergic receptors, in BCP's antidepressive-like activity. Furthermore, BCP increased BDNF levels in the hippocampus after 14 days of treatment. No treatments in this study altered locomotor activity in the open field test. CONCLUSION: This study provides a new mechanism of BCP-induced antidepressant-like effect mediated by some sub-types of catecholaminergic neurotransmitter system that could be a candidate for clinical tests of new treatments for depressive disorders.

Tert-butyl 4-((1-phenyl-1H-pyrazol-4-yl) methyl) piperazine-1-carboxylate (LQFM104)- New piperazine derivative with antianxiety and antidepressant-like effects: Putative role of serotonergic system.

The piperazine derivatives correspond to an extensive chemical class of compounds with numerous neuropharmacological activities, including antidepressant (e.g., nefazodone, trazodone) and anxiolytic (e.g., buspirone) properties. Therefore, aiming to identify a new antidepressant and antianxiety lead-compound, our group designed, synthesized, and investigated the effects of a new piperazine compound, namely, LQFM104, on the behavior of mice. Male albino Swiss mice were treated with LQFM104 prior to predictive behavioral tests as open field (OFT), elevated plus maze (EPM), forced swimming (FST), and tail suspension tests (TST). The participation of the serotonergic system was evaluated by pretreatment with a 5-HT1A antagonist receptor (WAY100635) and serotonin (5-HT) synthesis inhibitor (p-chlorphenylalanine, pCPA) before oral administration of LQFM104 and behavioral tests. The treatment with LQFM104 did not interfere with locomotor activity but revealed suggestive data of anxiolytic-like effects by the increase in the time spent in the center of the OFT. This activity was confirmed by the results obtained in the EPM, and it was abolished after pretreatment with WAY100635 and pCPA. The immobility time decreased in both the FST and TST. The antidepressant-like activity was completely abolished after WAY100635 pretreatment. Altogether, these data revealed that LQFM104 possesses anxiolytic and antidepressant-like properties in behavioral tests on mice, and these activities are possibly mediated, directly and/or indirectly, by serotonergic pathways.

Involvement of the monoamine system in antidepressant-like properties of 4-(1-phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester.

AIMS: Piperazinic derivatives have therapeutic potential by acting as analgesic, antidepressant-like, anticonvulsant and antipsychotic in preclinical studies. In order to develop new drugs to treat mental disorders, we designed and synthesized the 4-(1-phenyl-1H-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester (PPMP), a new piperazine derivative with putative activities on central nervous system that seems to involve serotonergic system. MATERIALS AND METHODS: In order to investigate the antidepressant-like activity of PPMP, mice were treated acutely and tested in the forced swimming test (FST) and tail suspension test. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., 4 days), and the non-selective blocker of catecholamine synthesis α-methyl para-tyrosine (AMPT, 100 mg/kg, i.p.) were used to assay the involvement of serotonergic and catecholaminergic systems. "Ex vivo" monoamine oxidase (MAO) enzymatic assay and quantification of hippocampal level of brain derived neurotrophic factor (BDNF) were carried out. KEY FINDINGS: PPMP reduced the immobility time in both tests. PCPA or AMPT (100 mg/kg, i.p.) pretreatment blocked the effects of PPMP, thereby suggesting the involvement of serotonergic and catecholaminergic systems in the antidepressant-like effect of PPMP. PPMP did not inhibit the activity of MAO. Moreover, after 14 days of treatment, PPMP 15 mg/kg/day induced antidepressant-like effect and increased hippocampal level of BDNF. None of the treatments in this study altered the locomotor activity in the open field test. SIGNIFICANCE: In conclusion, PPMP demonstrates antidepressant-like effect that involve both serotonergic and catecholaminergic systems without inhibition of MAO activity. PPMP administration increased the hippocampal levels of BDNF.

Mechanisms involved in the gastroprotective activity of Celtis iguanaea (Jacq.) Sargent on gastric lesions in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Celtis iguanaea (Canabaceae) is popularly known as esporão-de-galo, stands out among the medicinal plants used for treatment of gastric ulcers. In Brazil, the leaves they are used traditionally in infusion forms as an analgesic, antiasthmatic, digestive and diuretic. AIM OF THE STUDY: The present study was aimed to investigate the antiulcer mechanisms of hexane extract Celtis iguanaea leaves (HE) in several induced-gastric ulcer and characterize its chemical composition. MATERIALS AND METHODS: The HE was obtained by exhaustive extraction in Soxhlet apparatus. The chemical characterization of HE was performed by Electrospray Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) analysis. Mice were used for the evaluation of the gastroprotective activity. HE was analyzed in the HCl/ethanol, hypothermic restraint stress ulcer and acetic acid. In the investigation of the gastroprotective mechanisms of HE, were performed the amount of adhered gastric mucus, participation of the α2-adrenoceptor, nitric oxide (NO) and prostaglandins (PGs) using the HCl/ethanol-induced gastric mucosa lesion model. RESULTS: ESI FT-ICR MS analysis of HE suggest the presence of compounds as lipids, sterol lipids, steroids glycosides and polyphenol glycosides. The oral administration of HE at doses of 100 mg/kg or 200 mg/kg was able to protect the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and HE at dose of 100mg/kg protected against hypothermic-restraint stress and acetic -induced gastric lesions. The pretreatment with Yoimbine (2mg/kg, s.c.), an antagonist α2-adrenergic, L-NAME (20mg/kg, s.c.), an inhibitor of nitric oxide synthesis or indomethacin (10mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the gastroprotective activity of HE (100mg/kg, p.o.). CONCLUSIONS: Our results suggest that the Celtis iguanaea HE exhibits gastroprotective activity in different gastric ulcer models. The mechanism of gastroprotective effect of Celtis iguanaea HE suggests the participation of mucus as well as the involvement of α2-adrenergic receptors, NO and prostaglandins. The hydroxyl-linolenic acid, linoleic acids and conjugated oxo-linoleic acids are among the phytoconstituents that were identified in the Celtis iguanaea HE.

Anxiolytic and antidepressant like effects of natural food flavour (E)-methyl isoeugenol.

(E)-methyl isoeugenol (MIE) is a natural food flavour that constitutes 93.7% of an essential oil from Pimenta pseudocaryophyllus leaf. The leaf extracts of this species are used as a calming agent. As a ubiquitous food additive, the application of MIE for treating mood disorders appears to be globally attractive. Hence, we sought to evaluate general pharmacological activities, anticonvulsant, anxiolytic and antidepressant effects and the possible mechanisms of MIE actions. Administration of MIE was carried out prior to the exposure of a male Swiss mice to general behavioural tests, barbiturate sleep, PTZ-induced convulsion, light dark box (LDB), elevated plus maze (EPM), wire hanging, open field (OF) and forced swimming test (FST). The involvement of monoamine system was studied by mice pretreatment with WAY100635 (antagonist of 5-HT1A), α-methyl-p-tyrosine (AMPT; depletor of catecholamine) or p-chlorophenylalanine (PCPA; depletor of serotonin storage). There was no record of neurotoxic effect or animal's death during the course of general pharmacological tests. MIE at 250 and 500 mg kg(-1) potentiated the hypnotic effect of sodium pentobarbital. However, MIE did not protect against PTZ-induced convulsion. Except for MIE at 500 mg kg(-1), parameters evaluated in the LDB, EPM and OF demonstrated an anxiolytic like property of MIE. This effect was blocked by WAY100635 pretreatment. MIE at 500 mg kg(-1) elicited a reduction in locomotor activity of the mice in the OF. Anti-immobility effect of MIE 250 mg kg(-1) in the FST suggested an antidepressive like property. Unlike AMPT, pretreatment with PCPA reversed the antidepressant like effect of MIE. Our findings demonstrated anxiolytic and antidepressant like properties of (E)-methyl isoeugenol and suggested the participation of serotonergic pathways.

Anti-inflammatory effect of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol, a new derivative of 4-nerolidylcatechol.

OBJECTIVES: We have investigated the anti-inflammatory and antinociceptive effects of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol (LQFM-015), which was designed through molecular simplification strategy from 4-nerolidylcatechol. METHODS: The possible anti-inflammatory and antinociceptive effects were assayed on carrageenan-induced paw oedema and pleurisy, acetic acid-induced abdominal writhing and formalin tests in mice. KEY FINDINGS: LQFM-015 reduced the activity of PLA2 enzyme in vitro by 18%. Docking studies into the catalytic site of PLA2 were used to identify the binding mode of the LQFM-015. LQFM-015 showed a moderate antinociceptive effect, since this compound reduced the number of writhings by approximately up to 40% in the acetic acid-induced pain model; this antinociceptive activity also emerged in the second phase of the formalin-induced pain model (58% of inhibition). The anti-inflammatory action of LQFM-015 was confirmed in acute inflammation models, in which it reduced the formation of oedema to 52.78 ± 8.6 and 46.64 ± 5.2 at the second and third hour of carrageenan-induced paw oedema, respectively. Also in the carrageenan-induced pleurisy model, LQFM-015 reduced the migration of leucocytes by 26.0% and decrease myeloperoxidase activity by 50%. LQFM-015 showed different concentrations to inhibit 50% of isoenzyme cyclooxygenase activity (IC50); COX-1 IC50 = 36 µM) and COX-2 IC50 = 28 µM. CONCLUSIONS: LQFM-015 demonstrated inhibition of both PLA2 and COX enzymes; thus, the moderate antinociceptive effect of this compound could be attributed to its anti-inflammatory activity.

Preliminary studies of gastroprotective effect of Celtis iguanaea (Jacq.) Sargent leaves (Ulmaceae).

Antiulcerogenic activity of crude ethanolic extract of Celtis iguanaea leaves (CEE) was observed with experimental models such as ethanol, indomethacin, stress and pyloric ligation-induced gastric ulcers. Results obtained from indomethacin-induced ulcer showed the hexane fraction (HF) as the active fraction of CEE. This fraction inhibits the gastric acid secretion, increasing the gastric pH, decreasing the gastric acidity and total gastric contents. Neither the CEE nor the HF alters intestinal motility, thereby excluding a cholinergic antagonist mechanism. Further studies need to be conducted with HF in order to elucidate the active principle and the pharmacological mechanism involved.

The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, ß-caryophyllene, in male mice.

Spiranthera odoratissima A. St. Hil. (manacá) is used in folk medicine to treat renal and hepatic diseases, stomachache, headaches and rheumatism. A central nervous system (CNS) depressant effect of the hexane fraction from the ethanolic extract of this plant has been described. ß-caryophyllene, the main component of this essential oil, is a sesquiterpene compound with anti-inflammatory properties that has been found in essential oils derived from several medicinal plants. This work is aimed to evaluate the pharmacological activity of the essential oil obtained from S. odoratissima leaves (EO) and its major component on the murine CNS; we aimed to evaluate a possible anxiolytic-like effect and the underlying mechanisms involved. In an open field test, EO (500 mg/kg) and ß-caryophyllene (50, 100 and 200 mg/kg) increased the crossing frequency (P<0.05) and, EO (250 and 500 mg/kg) and ß-caryophyllene (200 mg/kg) increased the time spent in the center (P<0.05) without altering total crossings of the open field. EO and ß-caryophyllene did not alter the number of falls in the rota-rod test (P>0.05). In the pentobarbital-induced sleep test, EO (500 mg/kg) and ß-caryophyllene (200 and 400 mg/kg) decreased the latency to sleep (P<0.05), and EO (125, 250 and 500 mg/kg) (P<0.001) and ß-caryophyllene (200 and 400 mg/kg) (P<0.05 and P<0.001) increased the sleep time. In anxiety tests, EO (500 mg/kg) and ß-caryophyllene (100 and 200 mg/kg) increased head-dipping behavior (P<0.05) in the hole-board test, entries (P<0.05) into and time spent (P<0.05) on the open arms of the elevated plus maze (EPM), and number of transitions (P<0.05) and time spent in the light compartment (P<0.05) of a light-dark box (LDB). We further investigated the mechanism of action underlying the anxiolytic-like effect of EO and ß-caryophyllene by pre-treating animals with antagonists of benzodiazepine (flumazenil) and 5-HT(1A) (NAN-190) receptors prior to evaluation using EPM and LDB. The anxiolytic-like effects of EO were significantly reduced by pre-treatment with NAN-190 (P<0.05) but not flumazenil (P>0.05). The anxiolytic-like effects of ß-caryophyllene were not blocked by either NAN-190 or flumazenil (P>0.05). In conclusion, these results suggest that the essential oil derived from S. odoratissima produces an anxiolytic-like effect without altering motor performance and that this effect is mediated by 5-HT(1A) but not via benzodiazepine receptors. In addition, the major component, ß-caryophyllene, also has an anxiolytic-like effect that may contribute to the effects of EO, but this effect does not seem to be mediated via 5-HT(1A) or benzodiazepine receptors.

Central pharmacological activity of a new piperazine derivative: 4-(1-phenyl-1h-pyrazol-4-ylmethyl)-piperazine-1-carboxylic acid ethyl ester.

AIMS: Our study focuses on the design and synthesis of a new piperazinic derivate, 4-(1-phenyl-1h-Pyrazol-4-Ylmethyl)-Piperazine-1-Carboxylic Acid Ethyl ester (LQFM008), and evaluation of its anxiolytic-like profile in Swiss mice. MAIN METHODS: LQFM008 was evaluated in a screening test of the central nervous system including the rota-rod, sodium pentobarbital-induced sleep, open field, elevated plus maze and light-dark box tests. KEY FINDINGS: LQFM008 induced convulsions at the dose of 1.1 mmol/kg (i.p., s.c. or p.o.). LQFM008 up to 400 µmol/kg had no effect in the rota rod test. In the open field test, LQFM008 increased the number of crossings and the time spent at the central area as well as the sleeping time in sodium pentobarbital-induced sleep. In the elevated plus maze and light-dark box tests, this compound showed an anxiolytic-like activity. This anxiolytic-like activity was antagonized by NAN-190 (5-HT(1A) antagonist) but not by flumazenil (benzodiazepine antagonist). SIGNIFICANCE: The compound LQFM008 showed anxiolytic-like activity which may involve serotonergic pathway.

Involvement of 5-HT1A in the anxiolytic-like effect of dichloromethane fraction of Pimenta pseudocaryophyllus.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal applications of Pimenta pseudocaryophyllus infusion as a diuretic and aphrodisiac agent as well as tranquilizer in the form of tea for the treatment of emotional tension in Brazilian folk medicine has been in practice since time immemorial. Despite its popular therapeutic acceptance and claims, there are scanty scientific reports to corroborate its central biological activities. AIM: To characterize anxiolytic-like effect of the dichloromethane fraction (DF) obtained from ethanolic leaf extract of the Pimenta pseudocaryophyllus and identify mechanisms of action involved while seeking to support its popular use as a soothing agent. MATERIAL AND METHODS: Mice (25-35 g) were treated orally with DF obtained from ethanolic leaf extract of Pimenta pseudocaryophyllus and were submitted to light-dark box (LDB) and elevated plus maze (EPM) tests. Different groups of mice were treated with flumazenil and NAN-190 to identify mechanisms of action involved in the anxiolytic-like effect of DF. RESULTS: Treatment with DF increased number of transitions and time spent in the light compartment of the LDB while the time spent and numbers of entries in the open arm of the LCE were significantly increased. Pre-treatment of the animal with flumazenil (2 mg/kg, i.p.--competitive antagonist of benzodiazepine site of GABA(A) receptor) did not block this effect, thereby excluding participation of benzodiazepine site of the GABA(A) receptor. However, anxiolytic-like effect of DF was reversed by pre-treatment with NAN-190 (0.5 mg/kg, i.p.--an antagonist of the 5-HT(1A) receptor) thereby suggesting involvement of 5-HT(1A) receptor. The thin layer chromatography and high-performance liquid chromatography analysis indicated the predominance of (E)-methyl isoeugenol and oleanolic acid in DF. CONCLUSION: These results support the popular use of Pimenta pseudocaryophyllus as a calming agent and suggest the involvement of 5-HT(1A) receptor.

Anti-inflammatory effect of Spiranthera odoratissima A. St.-Hil. leaves involves reduction of TNF-α.

Spiranthera odoratissima A. St.-Hil., 'manacá', is a medicinal species used in Brazil, especially in central region, for the treatment of several diseases such as pain and inflammation. In this study, the methanol/aqueous phase of the ethanol extract of the leaves of 'manacá' (MAP), at the doses of 50, 150 and 500 mg/kg was used to evaluate the anti-inflammatory and/or antinociceptive effects and the possible anti-inflammatory mechanism. The antinociceptive and anti-inflammatory activities of MAP were assessed using formalin test, carrageenan-induced paw oedema. The myeloperoxidase activity, capillary permeability, leukocyte migration and tumour necrosis factor alpha (TNF-α) levels were evaluated in pleural exudate. The MAP reduced the licking time only in the later phase of formalin test, and showed anti-inflammatory activity by reducing the paw oedema, migration cell, myeloperoxidase activity, capillary permeability and TNF-α levels. In conclusion, we confirmed the inflammatory activity of MAP and affirm that this effect involves the reduction of TNF-α level.

Triterpenes involved in the anti-inflammatory effect of ethanolic extract of Pterodon emarginatus Vogel stem bark.

Bioassay-guided fractionation of the ethanolic extract of Pterodon emarginatus Vogel stem bark (EtEx) resulted in the isolation and characterization of lupeol and betulin. Their structures were elucidated by spectroscopic methods including IR, (1)H-NMR, (13)C-NMR and comparison with literature values. This study showed the anti-inflammatory activity of EtEx, the hexane (HexL) and dichloromethane (DichL) layers, and lupeol and betulin. The extract, HexL, DichL, lupeol and betulin were able to inhibit acetic acid-induced writhing. In the formalin test, EtEx decreased licking time only in the second phase characterizing anti-inflammatory activity. In the oil-induced ear oedema test, EtEx, lupeol and betulin decrease edema formation. In conclusion, EtEx has antinociceptive effects arising from anti-inflammatory activity; this activity could be due to the presence of lupeol and betulin.

Antinociceptive effect of Lafoensia pacari A. St.-Hil. independent of anti-inflammatory activity of ellagic acid.

This study was performed to determine the antinociceptive and anti-inflammatory activities of ethanolic extract of Lafoensia pacari A. St.-Hil. (PEtExt) stem bark and its fractions using various animal models such as acetic acid-induced abdominal writhing, formalin-induced pain and croton oil-induced ear edema tests. The PEtExt inhibited the acetic acid-induced abdominal writhing, reduced the pain reaction time on both phases of the formalin test and decreased the edema in a dose-dependent manner. Pre-treatment with naloxone did not reverse the antinociceptive effect. Only the ethyl acetate fraction showed antinociceptive and anti-inflammatory effects. Our results also showed that this extract contains compounds with analgesic action independent of anti-inflammatory activity.

Central activities of hydroalcoholic extract from Lafoensia pacari A. St.-Hil. stem bark / Atividades centrais do extrato de Lafoensia pacari A. St.- Hil. da casca do caule

Lafoensia pacari A. St.-Hil. can be found from Amapá to Rio Grande do Sul states, and also in Paraguay and Bolivia. It is popularly known as pacari or mangava-brava and is used to promote weight loss, as an anti-thermal or tonic, to treat gastritis, ulcers, scarring, itching, discouragement, and cancer. In the open field tests, the hydroalcoholic extract from L. pacari stem bark (HEP) decreased the number of rearings, number of invaded squares, and increased immobility time compared to control animals. In the pentobarbital-induced sleep time test, HEP decreased latency time to sleep and increased sleeping time. In the rota-rod test, no changes in the studied parameters were observed. In the elevated plus maze, HEP increased the percentage time and percentage entries in the open arms, indicating that this extract exerts an anxiolytic-like activity.

Lafoensia pacari A. St.-Hil., uma espécie vegetal presente no Brasil, do Amapá ao Rio Grande do Sul, no Paraguai e na Bolívia, é popularmente conhecida como pacari ou mangava-brava e é utilizada como emagrecedor, cicatrizante, antitérmico, tônico e para tratar gastrite, úlcera, coceira, desânimo e câncer. No teste do campo aberto, o tratamento com o extrato hidro-alcoólico de pacari (HEP) reduziu o número de rearings e o número de quadrados invadidos além de aumentar o tempo de imobilidade dos animais em relação ao controle. No sono induzido por pentobarbital sódico o tratamento com HEP causou redução na latência e aumento na duração do sono. No rota-rod, o tratamento com HEP não alterou os parâmetros observados. No teste de labirinto em cruz elevado, com o tratamento com HEP foi observado aumento do percentual do tempo de permanência e de entradas nos braços abertos, caracterizando uma atividade tipo ansiolítica.

Effects of ethanolic extract of leaves of Lafoensia pacari A. St.-Hil., Lythraceae (pacari), in pain and inflammation models / Efeitos do extrato etanólico das folhas de Lafoensia pacari A. St.-Hil., Lythraceae (pacari), em modelos de dor e inflamação

Lafoensia pacari A. St.-Hil., Lythraceae, popularly known as pacari, is a Cerrado's native specimen; the stem bark extract is used in folk for pain and inflammation, also showing sedating activity. This study aimed to evaluate the analgesic and anti inflammatory activities of ethanol extract from pacari leaves (EEPL). These activities were verified in mice. The previous treatment with EEPL 1.0 g/kg showed antinociceptive activity both in the acetic acid-induced writing test and in the formalin-induced model of pain, and in neurogenic and inflammatory phases as well. In the croton oil-induced ear edema, the pre-treatments with EEPL reduced the edema in a dose-dependent manner. Also in the carrageenan-induced peritonitis, the two major doses tested (2.0 and 1.5 g/kg p.o.) were able to reduce the leukocyte migration in a dose-dependent manner. The Central Nervous System tests showed that the extract does not elicit uncoordinated motricity, hypnosis or sedating effects. The results showed that EEPL maintains the analgesic and anti-inflammatory effects of the stem bark of pacari, being the collect of leaves more favorable to the preservation of this Cerrado's native specimen.

O pacari (Lafoensia pacari A. St.-Hil., Lythraceae) é uma espécie vegetal nativa do cerrado, o extrato da casca de caule é utilizado popularmente para dores e inflamação, tendo mostrado atividade sedativa. Este trabalho objetivou avaliar os efeitos do extrato etanólico das folhas do pacari (EEFP) como analgésico e antiinflamatório. As atividades analgésica e antiinflamatória foram verificadas em camundongos. O tratamento prévio com EEFP 1,0 g/kg mostrou atividade antinociceptiva tanto no método das contorções abdominais induzidas por ácido acético como também no modelo de dor induzida por formalina, tanto na fase neurogênica quanto na fase inflamatória. Os pré-tratamentos com o EEFP reduziram o edema de orelha, induzido por óleo de cróton, de forma dose-dependente. Os testes de atividade no sistema nervoso central mostraram que o extrato não provoca incoordenação motora nem hipnose ou sedação. Os resultados mostram que o EEFP mantém as atividades analgésica e antiinflamatória do extrato das cascas do caule do pacari, sendo que a coleta das folhas favorece a preservação desta espécie nativa do cerrado.

Evaluation of the antinociceptive and anti-inflammatory effects of the acetone extract from Anacardium occidentale L / Avaliação dos efeitos antinociceptivo e antiinflamatório do extrato acetônico de Anacardium occidentale L

The stem bark of Anacardium occidentale L. (Anacardiaceae), commonly called cashew, is used in Brazilian traditional medicine for the treatment of gastric and inflammatory disorders. The present study was carried out to investigate the in vivo anti-inflammatory activities of the acetone extract (AE) of the stem bark of A. occidentale. We evaluated the pharmacological activities of this plant material through the analgesic, antiedematogenic and chemotaxic inhibitory effects produced by the AE. The oral administration (p.o.) of mice with the AE (0.1, 0.3 and 1.0 g/kg) or positive control indomethacin (10 mg/kg) inhibited acetic acid-induced writhing by 18.9, 35.9, 62.9 and 68.9 percent, respectively (ID50 percent = 530 mg/kg). The highest dose of the AE was able to inhibit croton oil-induced ear edema formation by 56.8 percent (indomethacin at 10 mg/kg, p.o. - 57.6 percent inhibition). When submitted to the carrageenan-induced peritonitis test, the AE (0.1, 0.3 and 1.0 g/kg, p.o.) impaired leukocyte migration into the peritoneal cavity by 24.8, 40.5 and 49.6 percent, respectively. The positive control, dexamethasone (2 mg/kg, s.c.), inhibited leukocyte migration by 66.9 percent. These results indicate the presence of anti-inflammatory and antinociceptive principles in the acetone extract of Anacardium occidentale, and reinforce the plant's potential therapeutic use against pain and inflammatory diseases.

As cascas do caule do Anacardium occidentale L. (Anacardiaceae), conhecido como cajueiro, são popularmente utilizadas no Brasil para o tratamento de doenças gástricas e inflamatórias. Este estudo teve como objetivo a avaliação farmacológica in vivo da atividade antiinflamatória do extrato acetônico (AE) obtido das cascas do A. occidentale, investigando os efeitos analgésico, antiedematogênico e inibitório sobre a quimiotaxia deste material botânico. A administração oral (p.o.) em camundongos com o AE (0,1; 0,3 e 1 g/kg) ou o controle positivo indometacina (10 mg/kg) inibiu as contorções abdominais induzidas pelo ácido acético em 18,9; 35,9; 62,9 e 68,9 por cento respectivamente (ID50 por cento = 530 mg/kg). Esta maior dose do AE também inibiu o edema de orelha produzido pelo óleo de cróton em 56,8 por cento (indometacina, 10 mg/kg, p.o. - 57,6 por cento de inibição). No teste da peritonite induzido pela carragenina, o AE (0,1; 0,3; e 1,0 mg/kg, p.o.) reduziu a migração de leucócitos para a cavidade peritoneal em 24,8; 40,5; e 49,6 por cento respectivamente, enquanto que o controle positivo dexametasona (2 mg/kg, s.c.) inibiu a migração de leucócitos em 66,9 por cento. Estes resultados indicam a presença de princípios ativos antiinflamatórios e antinociceptivos no extrato acetônico de Anacardium occidentale e reforçam o potencial terapêutico da planta em doenças que envolvem dor e inflamação.