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ABSTRACT: Antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels were tested using bioautographic and microdilution techniques against three plant pathogenic fungi (Penicillium digitatum, Curvularia sp., and Colletotrichum sp.), two human pathogens (Trichophyton mentagrophytes and Microsporum canis), and two opportunistic bacteria (Escherichia coli and Staphylococcus aureus). Two polymethoxylated flavonoids and a coumarin derivative, were isolated and identified from peel extracts, which presented antimi-crobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon.
Memórias do Instituto Oswaldo Cruz 02/2013; 102(6):681-685. · 2.15 Impact Factor
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ABSTRACT: A mixture of the two new flavonols 8-hydroxy-3,4',5,6,7-pentamethoxyflavone (1) and 8-hydroxy-3,3',4',5,6,7-hexamethoxyflavone (2) was isolated from a commercial sample of Citrus aurantifolia. An array of one-(1 HNMR, { 1 H}-13 C NMR, and APT-13 C NMR) and two-dimensional NMR techniques (COSY, NOESY, HMQC and HMBC) was used to achieve the structural elucidation and the complete 1 H and 13 C chemical shift assignments of these natural compounds. In addition, the antifungal activity of these compounds against phytopathogenic and human pathogenic fungi was investigated.
Anais da Academia Brasileira de Ciências 02/2013; 79:215-222. · 1.09 Impact Factor
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Daniele G Machado,
Mauricio P Cunha,
Vivian B Neis,
Grasiela O Balen,
André Colla,
Luis E B Bettio,
Agatha Oliveira,
Francis Leonardo Pazini,
Juliana B Dalmarco,
Edésio Luiz Simionatto, Moacir G Pizzolatti,
Ana Lúcia S Rodrigues
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ABSTRACT: The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.
Food Chemistry 01/2013; 136(2):999-1005. · 3.65 Impact Factor
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Andiara E Freitas,
Daniele G Machado,
Josiane Budni,
Vivian B Neis,
Grasiela O Balen,
Mark W Lopes,
Luiz F de Souza,
Patricia O Veronezi,
Melina Heller,
Gustavo A Micke, Moacir G Pizzolatti,
Alcir L Dafre,
Rodrigo B Leal,
Ana Lúcia S Rodrigues
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. AIM OF THE STUDY: To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice. MATERIALS AND METHODS: Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behaviour indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3β, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle. RESULTS: EET (10 and 30mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser(133)) and GSK-3β (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group. CONCLUSIONS: EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.
Journal of ethnopharmacology 12/2012; · 2.32 Impact Factor
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Daniele G Machado,
Mauricio P Cunha,
Vivian B Neis,
Grasiela O Balen,
André R Colla,
Jaine Grando,
Patricia S Brocardo,
Luis E B Bettio,
Juliana B Dalmarco,
Daniel Rial,
Rui D Prediger, Moacir G Pizzolatti,
Ana Lúcia S Rodrigues
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ABSTRACT: Rosemary, Rosmarinus officinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression.
To evaluate the ability of Rosmarinus officinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice.
Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle.
ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE.
ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.
Journal of ethnopharmacology 06/2012; 143(1):158-69. · 2.32 Impact Factor
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Eduardo L. G. Moreira,
Daniel Rial,
Aderbal S. Aguiar,
Cláudia P. Figueiredo,
Jarbas M. Siqueira,
Silvia DalBó,
Heros Horst,
Jade de Oliveira,
Gianni Mancini,
Tiago S. dos Santos,
Jardel G. Villarinho,
Francielle V. Pinheiro,
José Marino-Neto,
Juliano Ferreira,
Andreza F. De Bem,
Alexandra Latini, Moacir G. Pizzolatti,
Rosa M. Ribeiro-do-Valle,
Rui D. S. Prediger
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ABSTRACT: We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered
impairments in olfactory, cognitive and motor functions associated with time-dependent disruption of dopaminergic neurotransmission
in different brain structures conceivably analogous to those observed during different stages of Parkinson’s disease (PD).
On the other hand, the proanthocyanidin-rich fraction (PRF) obtained from the bark of Croton celtidifolius Baill (Euphorbiaceae), a tree frequently found in the Atlantic forest in south Brazil, has been described to have several
neurobiological activities including antioxidant and anti-inflammatory properties, which may be of interest in the treatment
of PD. The present data indicated that the pretreatment with PRF (10mg/kg, i.p.) during five consecutive days was able to
prevent mitochondrial complex-I inhibition in the striatum and olfactory bulb, as well as a decrease of the enzyme tyrosine
hydroxylase expression in the olfactory bulb and substantia nigra of rats infused with a single intranasal administration
of MPTP (1mg/nostril). Moreover, pretreatment with PRF was found to attenuate the short-term social memory deficits, depressive-like
behavior and reduction of locomotor activity observed at different periods after intranasal MPTP administration in rats. Altogether,
the present findings provide strong evidence that PRF from C. celtidifolius may represent a promising therapeutic tool in PD, thus being able to prevent both motor and non-motor early symptoms of PD,
together with its neuroprotective potential.
KeywordsMPTP-Intranasal-Parkinson’s disease-Catechin-Proanthocyanidin-
Croton celtidifolius
-Neuroprotection-Behavior-Rat
Acta Neurovegetativa 04/2012; 117(12):1337-1351. · 2.73 Impact Factor
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ABSTRACT: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential.
The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST).
Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract.
The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01-30 mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1 mg/kg, i.p., α₂-adrenoceptor antagonist), propranolol (1 mg/kg, i.p., β-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., dopamine D₁ receptor antagonist) or sulpiride (50 mg/kg, i.p., dopamine D₂ receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30 mg/kg). Moreover, ketanserin (5 mg/kg, i.p., preferential 5-HT(2A) receptor antagonist) enhanced the effect of the extract in FST.
The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT2A receptors), noradrenergic (α₂ and β-receptor) and dopaminergic (D₁ and D₂ receptors) systems.
Pharmaceutical Biology 12/2011; 49(12):1277-85. · 0.88 Impact Factor
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Luciana de Carvalho Tavares,
Susana Johann,
Tânia Maria de Almeida Alves,
Juliana Correia Guerra,
Elaine Maria de Souza-Fagundes,
Patrícia Silva Cisalpino,
Adailton J Bortoluzzi,
Giovanni F Caramori,
Rafael de Mattos Piccoli,
Hugo T S Braibante,
Mara E F Braibante, Moacir G Pizzolatti
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ABSTRACT: A series of new 6-quinolinyl and quinolinyl N-oxide chalcones were efficiently prepared. All chalcones were tested by minimal inhibitory concentration (MIC) against three species of Candida, Cryptococcus gattii and Paracoccidioides brasiliensis. The effect of these compounds was also tested on the survival and growth of the human cancer cell lines UACC-62 (melanoma), MCF-7 (breast), TK-10 (renal) and leukemic cells, Jurkat and HL60. The compounds tested presented strong activity against P. brasiliensis, most importantly compound 4e. C. gattii also presented interesting susceptibility for compounds 5b and 5f. The cytotoxic activity showed that compounds 3c and 4e, presented the best activity against MCF-7 and TK-10. For leukemic cells the compounds 4f, 3g, 4g and 5g have shown the best activity.
European journal of medicinal chemistry 07/2011; 46(9):4448-56. · 3.27 Impact Factor
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ABSTRACT: In the present study, we investigated the potential protective effects of three flavonoids (myricetin, myricitrin and rutin) derived from medicinal plants against methyl mercury (MeHg)-induced mitochondrial dysfunction in vitro. Incubation of mouse brain mitochondria with MeHg induced a significant decrease in mitochondrial function, which was correlated with decreased glutathione (GSH) levels and increased generation of reactive oxygen species (ROS) and lipid peroxidation. The co-incubation of mouse brain mitochondria with myricetin or myricitrin caused a concentration-dependent decrease of MeHg-induced mitochondrial dysfunction and oxidative stress. The flavonoid rutin was ineffective in counteracting MeHg toxicity. Among the three tested flavonoids, myricetin was the most efficient in protecting against MeHg-induced mitochondrial dysfunction. Moreover, myricetin completely blocked MeHg-induced ROS formation and lipid peroxidation and partially prevented MeHg-induced GSH depletion. The ability of myricetin to attenuate MeHg-induced mitochondrial dysfunction and oxidative stress appears to be related to its higher scavenging capability when compared to myricitrin and rutin. Overall, the results suggest that MeHg-induced mitotoxicity is associated with oxidative stress. The ability of myricetin to prevent MeHg-induced oxidative damage in brain mitochondria renders this flavonoid a promising molecule for further in vivo studies in the search for potential antidotes to counteract MeHg-induced neurotoxicity.
Environmental Toxicology and Pharmacology. 11/2010;
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ABSTRACT: The relationship between depression and monoaminergic systems has been hypothesized for many years. In this study, we have investigated the possible antidepressant-like effect of scopoletin, a coumarin from Polygala sabulosa in the tail suspension test and forced swimming test. Moreover, the ability of scopoletin to reverse the depression-like behavior in the forced swimming test induced by immobility stress in mice was evaluated. Scopoletin reduced the immobility time in the tail suspension test (10-100mg/kg, p.o.), but not in the forced swimming test. Fluoxetine (positive control) decreased the immobility time in the forced swimming and tail suspension tests (20mg/kg, p.o. and 10mg/kg. p.o., respectively). Immobility stress caused an increase in the immobility time in the forced swimming test (depression-like behavior), which was reversed by scopoletin (1-100mg/kg, p.o.) and fluoxetine (10mg/kg, p.o.). Scopoletin produced no psychostimulant effect in the open-field test. The pretreatment of mice with ketanserin (5mg/kg, i.p., a preferential 5-HT(2A) receptor antagonist), prazosin (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), haloperidol (0.2mg/kg, i.p., a dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist), but not WAY100635 (0.1mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) prevented the antidepressant-like effect of scopoletin (10mg/kg, p.o.) in the tail suspension test. The results indicate that its antidepressant-like effect is dependent on the serotonergic (5-HT(2A) receptors), noradrenergic (alpha(1)- and alpha(2)-adrenoceptors) and dopaminergic (dopamine D(1) and D(2) receptors) systems.
European journal of pharmacology 09/2010; 643(2-3):232-8. · 2.59 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the possible neurobehavioural effects in rats of the proanthocyanidin-rich fraction (PRF) isolated from the bark of Croton celtidifolius (Euphorbiaceae).
Adult Wistar rats were treated with the PRF (0.3-30 mg/kg) and evaluated in different behavioural paradigms classically used for the screening of drugs with psychoactive effects.
Acute intraperitoneal (i.p.) administration of PRF decreased spontaneous locomotor activity (open field arena and activity cage), enhanced the duration of ethyl ether-induced hypnosis, increased the latency to the first convulsion induced by pentylenetetrazole (60 mg/kg, i.p.) and attenuated apomorphine-induced (0.5 mg/kg, i.p.) stereotyped behaviour. In lower doses, PRF (0.3 or 3 mg/kg, i.p.) increased the frequency of open arm entries in the elevated plus-maze test.
The present findings suggest that the systemic administration of PRF induces a wide spectrum of behavioural alterations in rats, consistent with the putative existence of hypnosedative, anticonvulsant and anxiolytic compounds.
The Journal of pharmacy and pharmacology. 08/2010; 62(8):1061-8.
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ABSTRACT: ETHNOPHARMACOLOGYCAL RELEVANCE: The tea from the leaves of Baccharis illinita DC (Asteraceae family) is commonly used by the population as anti-inflammatory (including topically), protective gastric and anti-infectious. However, no studies have been done with this species to confirm its topical anti-inflammatory action.
This study evaluated he topical effects of crude extract of leaves (CE) and its active constituents in 12-O-tetradecanoylphorbol acetate (TPA)-induced ear oedema.
CE and compounds effects were tested in commonly used models of TPA-, arachidonic acid (AA)- and capsaicin-ear oedema. Polymorphonuclear (PMN) cell migration was evaluated by mieloperoxidase and analyzed histologically.
CE (0.1-1 mg/ear) caused a dose-related inhibition of TPA-induced ear oedema and PMN influx similarly to that produced by topical application of the steroidal anti-inflammatory drug dexamethasone. The active constituents of the AcOEt fraction kaurenoic acid, alpha-spinasterol, oleanolic acid and baurenol also inhibited TPA-induced ear edema. Histological analysis of the ear of CE-treated animals confirmed the reduction of edema and of PMN infiltration. Both CE and the nosteroidal anti-inflammatory drug indomethacin inhibited the AA-induced ear oedema, but did not change capsaicin-induced oedema.
These results indicate that the CE and the active constituents have a topical anti-inflammatory effect and the possible mechanisms for the pharmacological effects are discussed.
Journal of ethnopharmacology 05/2010; 130(2):262-6. · 2.32 Impact Factor
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ABSTRACT: The antidepressant-like effect of the ethanolic extract obtained from barks of Tabebuia avellanedae, a plant widely employed in folk medicine, was investigated in two predictive models of depression: forced swimming test (FST) and tail suspension test (TST) in mice. Additionally, the mechanisms involved in this antidepressant-like action and the effects of the association of the extract with the antidepressants fluoxetine, desipramine and bupropion in the TST were investigated. The extract from T. avellanedae produced an antidepressant-like effect, in the FST (100 mg/kg, p.o.) and in the TST (10-300 mg/kg, p.o.), without accompanying changes in ambulation when assessed in the open-field test. The anti-immobility effect of the extract (30 mg/kg, p.o.) in the TST was prevented by pre-treatment of mice with ketanserin (5 mg/kg, i.p., a preferential 5-HT(2A) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a beta-adrenoceptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist) and SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist). The combined administration of a subeffective dose of WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) and a subeffective dose of the extract (1 mg/kg, p.o.) produced a significant reduction in the immobility time in the TST. In addition, the combination of fluoxetine (1 mg/kg, p.o.), desipramine (0.1 mg/kg, p.o.), or bupropion (1 mg/kg, p.o.) with a subeffective dose of the extract (1 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing hyperlocomotion in the open-field test. It may be concluded that the extract from T. avellanedae produces an antidepressant-like effect in the FST and in the TST that is dependent on the monoaminergic system. Taken together, our results suggest that T. avellanedae deserves further investigation as a putative alternative therapeutic tool that could help the conventional pharmacotherapy of depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2009; 34(2):335-43. · 3.25 Impact Factor
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Cristina Setim Freitas,
Cristiane Hatsuko Baggio,
Ana Cristina Dos Santos,
Bárbara Mayer,
André Twardowschy,
Ana Paula Luiz,
Rodrigo Marcon,
Cristian Soldi, Moacir G Pizzolatti,
Elide Pereira Dos Santos,
Maria Consuelo Andrade Marques,
Adair R S Santos
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ABSTRACT: The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
Basic & Clinical Pharmacology & Toxicology 05/2009; 104(4):285-92. · 2.18 Impact Factor
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ABSTRACT: The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (acetic-acid, formalin, capsaicin, cinnamaldehyde and glutamate tests) and thermal (tail-flick and hot-plate test) models of pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of excitatory amino acids receptors glutamate and cytokines such as interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) in mice. When given orally, hydroalcoholic extract (0.001-10 mg/kg), produced potent and dose-dependent inhibition of acetic acid-induced visceral pain. In the formalin test, the hydroalcoholic extract (0.0001-0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. However, it was more potent and efficacious in relation to the late phase of the formalin test. The capsaicin-induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the cinnamaldehyde-induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001-1.0 mg/kg orally) caused significant and dose-dependent inhibition of glutamate-induced pain. However, only rutin, but not phebalosin or aurapten, isolated from P. paniculata, administered intraperitoneally to mice, produced dose-related inhibition of glutamate-induced pain. Furthermore, the hydroalcoholic extract (0.1-100 mg/kg orally) had no effect in the tail-flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot-plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the glutamate test, was neither affected by intraperitoenal treatment of animals with l-arginine (precursor of nitric oxide, 600 mg/kg) and naloxone (opioid receptor antagonist, 1 mg/kg) nor associated with non-specific effects such as muscle relaxation or sedation. In addition, oral administration of hydroalcoholic extract produced a great inhibition of the pain-related behaviours induced by intrathecal injection of glutamate, N-methyl-D-aspartate (NMDA), IL-1beta and TNF-alpha, but not by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), kainate or trans-1-amino-1.3-cyclopentanediocarboxylic acid (trans-ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical pain used in this study.
Basic & Clinical Pharmacology & Toxicology 05/2009; 104(4):306-15. · 2.18 Impact Factor
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ABSTRACT: Rosemary, Rosmarinus officinalis L. (Labiatae) has several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including depression. In this study, the effect of the hydroalcoholic extract of the stems and leaves of this plant was investigated in two behavioral models, the forced swimming test (FST) and tail suspension test (TST) in mice. The extract of R. officinalis produced an antidepressant-like effect, since the acute treatment of mice with the extract by p.o. route significantly reduced the immobility time in the FST (100 mg/kg) and TST (10-100 mg/kg), as compared to a control group, without accompanying changes in ambulation in the open-field test. Moreover, the repeated administration (14 days) of the hydroalcoholic extract of R. officinalis by p.o. route also produced an antidepressant-like effect in the TST (100-300 mg/kg). The pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A) receptor antagonist), 1-(m-chlorophenyl) biguanide (mCPBG, 10 mg/kg, i.p., a 5-HT(3) receptor agonist), prazosin (1 mg/kg, i.p., an alpha(1-)adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), but not yohimbine (1 mg/kg, i.p., an alpha(2-)adrenoceptor antagonist) was able to reverse the anti-immobility effect of the extract (10 mg/kg, p.o.) in the TST. The combination of MDL72222, (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist) with a sub-effective dose of the extract of R. officinalis (1 mg/kg, p.o.) produced an anti-immobility effect in the TST. The results suggest that the antidepressant action of the extract of R. officinalis is mediated by an interaction with the monoaminergic system and that this plant should be further investigated as an alternative therapeutic approach for the treatment of depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2009; 33(4):642-50. · 3.25 Impact Factor
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Roberta de P Martins,
Hugo de C Braga,
Aline P da Silva,
Juliana B Dalmarco,
Andreza F de Bem,
Adair Roberto S dos Santos,
Alcir L Dafre, Moacir G Pizzolatti,
Alexandra Latini,
Michael Aschner,
Marcelo Farina
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ABSTRACT: Methylmercury (MeHg) is a highly neurotoxic pollutant, whose mechanisms of toxicity are related to its pro-oxidative properties. A previous report showed under in vivo conditions the neuroprotective effects of plants of the genus Polygala against MeHg-induced neurotoxicity. Moreover, the flavonoid quercetin, isolated from Polygala sabulosa, displayed beneficial effects against MeHg-induced oxidative damage under in vitro conditions. In this study, we sought for potential beneficial effects of quercetin against the neurotoxicity induced by MeHg in Swiss female mice. Animals were divided into six experimental groups: control, quercetin low dose (5 mg/kg), quercetin high dose (50 mg/kg), MeHg (40 mg/L, in tap water), MeHg+quercetin low dose, and MeHg+quercetin high dose. After the treatment (21 days), a significant motor deficit was observed in MeHg+quercetin groups. Biochemical parameters related to oxidative stress showed that the simultaneous treatment with quercetin and MeHg caused a higher cerebellar oxidative damage when compared to the individual exposures. MeHg plus quercetin elicited a higher cerebellar lipid peroxidation than MeHg or quercetin alone. The present results indicate that under in vivo conditions quercetin and MeHg cause additive pro-oxidative effects toward the mice cerebellum and that such phenomenon is associated with the observed motor deficit.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2009; 47(3):645-9. · 2.99 Impact Factor
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Camila M Ribas,
Flavia C Meotti,
Francisney P Nascimento,
Amanda V Jacques,
Alcir L Dafre,
Ana Lúcia S Rodrigues,
Marcelo Farina,
Cristian Soldi,
Beatriz G Mendes, Moacir G Pizzolatti,
Adair R S Santos
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ABSTRACT: This study investigated the role of the glutamatergic system on the antinociception caused by Polygala sabulosa hydroalcoholic extract (HE). The systems mediated by substance P, capsaicin, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) were also investigated. P. sabulosa HE given orally produced a significant inhibition of glutamate-induced paw licking [ID(50) = 530.3 (416.7-674.8) mg/kg and inhibition of 79 +/- 6% at 1000 mg/kg]. The plant derivatives alpha-spinasterol, scopoletin and styryl-2-pyrones (compound 1 and 3) (10 mg/kg, intraperitoneally) inhibited 80 +/- 7%, 46 +/- 11%, 45 +/- 11% and 35 +/- 13% the nociceptive response caused by glutamate, respectively. Furthermore, P. sabulosa HE (500 mg/kg, orally) caused marked inhibition of nociceptive response induced by intrathecal injection of glutamate, N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, TNF-alpha and IL-1beta, with inhibitions of 44 +/- 7%, 55 +/- 4%, 38 +/- 10%, 61 +/- 7%, 76 +/- 9% and 100%, respectively. In contrast, P. sabulosa HE (500 mg/kg, orally) did not affect the biting response induced by the metabotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P and capsaicin. The locomotor activity was altered only in mice treated with a very high dose (1000 mg/kg) of P. sabulosa HE. Our results showed that the antinociceptive effects of P. sabulosa HE are associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. The plant derivatives alpha-spinasterol, scopoletin and styryl-2-pyrones play an important role on the antinociceptive effects of P. sabulosa HE.
Basic & Clinical Pharmacology & Toxicology 08/2008; 103(1):43-7. · 2.18 Impact Factor
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ABSTRACT: Baccharis illinita DC (Compositae) is used in folk medicine to treat gastric disturbances. Preliminary studies with other extracts of B. Illinita showed gastric protection against ethanol-, indometacin- and stress-induced ulcers and the inhibition of gastric secretion. Based on these data, the aim of this study was to verify the pathways involved in the inhibition of gastric secretion. The chloroform extract (CE) of flowers from B. illinita (3, 10, 30 and 100 mg kg(-1) i.p.) tested on rats with pylorus ligature reduced the volume and the total acidity of gastric content by approximately 50% (ED50 = 69 mg kg(-1)). Treatment with CE (100 mg kg(-1) i.p.) reduced the gastric total acidity stimulated by histamine, bethanechol and pentagastrin to 42%, 27% and 57% of that in the stimulated control group, respectively. The CE (10, 30 and 100 microM) inhibited H+/K+ ATPase activity in-vitro, with an IC50 of 37 microM. The isolated flavonoid luteolin (1, 3, 10 and 30 microM) also inhibited H+/K+ ATPase activity by 50%, at a dose of 30 microM. Our results suggest that the reduction in gastric secretion occurs through inhibition of H+/K+ ATPase, which is the final step in acid secretion and therefore one of the most important steps.
Journal of Pharmacy and Pharmacology 08/2008; 60(8):1105-10. · 2.17 Impact Factor
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ABSTRACT: Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mg kg(-1)) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mg kg(-1) per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mg kg(-1)) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mg kg(-1)) inhibited total acidity by 50%, 60% and 67%, respectively. In-vitro, CE inhibited H+, K+ -ATPase activity with an EC50 of 53 microgmL(-1) and fraction A (30 and 100 microgmL(-1)) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 microgmL(-1)) and fraction B (100 and 250 microgmL(-1)) had free-radical scavenging ability, inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+ -ATPase.
Journal of Pharmacy and Pharmacology 07/2008; 60(6):795-801. · 2.17 Impact Factor
