The molecular modification and synthesis of compounds is vital to discovering drugs with desirabl... more The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorphenyl)-1H-pyrazol-4-yl]-2H-tetrazole (FPPT). During the acetic acid-induced abdominal writhing test, treatments with FPPT reduced abdominal writhing, while during the formalin test, FPPT reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. FPPT also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, FPPT exhibits a vasorelaxant effect attenuated by Nω-nitro-L-arginine methyl ester, 1H-[1,2, 4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. FPPT also blocked CaCl2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, FPPT reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2,000 mg/kg. Lastly, the…
Low quality of life and life-threatening conditions often demand pharmacological screening of lea... more Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.
Introducao e objetivos: Hydrocotyle umbellata L. Araliaceae (acaricoba) e planta utilizada na med... more Introducao e objetivos: Hydrocotyle umbellata L. Araliaceae (acaricoba) e planta utilizada na medicina popular brasileira por suas propriedades ansioliticas1. Este trabalho investigou o efeito tipo ansiolitico do extrato etanolico das partes subterrâneas de H. umbellata (E-HU) e das fracoes. Metodologia: O extrato e as fracoes foram obtidos conforme metodologia adaptada de Ferri, 19962. Foram utilizados camundongos Swiss machos adultos nos testes do labirinto em cruz elevado (LCE), sono induzido por pentobarbital, caixa claro escuro (CCE) e campo aberto. Resultados e discussoes: E-HU (1g/kg v.o.) demonstrou efeito tipo ansiolitico evidenciado pelo maior percentual de entradas (58,17 3,46%) e maior tempo gasto nos bracos abertos 155,8 12,16 s, no LCE em comparacao ao grupo controle (CTL = veiculo 10 mL/kg v.o.) 44,38 2,82% e 117,4 12,84 s, e um efeito sedativo representado pelo aumento na duracao do sono induzido por pentobarbital (E-HU: 87,70 5,94; CTL: 61,70 4,26 min). A...
Introdução e objetivos: Os compostos pirazolínicos são conhecidos por apresentar atividade anti-i... more Introdução e objetivos: Os compostos pirazolínicos são conhecidos por apresentar atividade anti-inflamatória, analgésica e antipirética. O objetivo deste trabalho foi avaliar o derivado pirazolínico LQFM 021, em testes nociceptivos crônicos de artrite induzida por CFA. Metodologia: Grupos de ratas (n=7) pré-sensibilizados foram tratados (v.o.) com veículo (10 mL/kg 1 vez/dia), LQFM 021 (15 mg/kg 2 vezes/dia) ou LQFM 021 (30 mg/kg 1 vez/dia). Uma hora após os tratamentos foi feito uma injeção intra-articular de CFA. Medidas do tempo de elevação da pata (TEP) e do diâmetro articular foram realizadas até o 6° dia. Resultados e discussões: Tratamento com LQFM 021 30 mg/kg 1 vez/dia promoveu uma redução progressiva e permanente do TEP a partir do 2° dia, em 26,3; 31,4; 31,3; 41,8 e 47,0 %. A formação do edema foi reduzida a partir do 1° dia de tratamento em 29,6; 15,6; 21,2; 29,2 e 29,5 %. Na migração celular, houve uma redução do número de leucócitos em 34,2 % e polimorfonucleares em 54...
Bioassay-guided fractionation of the ethanolic extract of Pterodon emarginatus Vogel stem bark (E... more 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.
The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAla... more The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAlafia multiflora Stapf(AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol aβ-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce signific...
The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAla... more The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAlafia multiflora Stapf(AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol aβ-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce signific...
CNS & neurological disorders drug targets, Jan 20, 2018
This study was conducted to evaluate the antidepressant-like activity of sesquiterpene compound β... more This study was conducted to evaluate the antidepressant-like activity of sesquiterpene compound β-caryophyllene (BCP) for the possible contribution of the monoamine and hippocampal levels of brain-derived neurotrophic factor (BDNF). 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. The anti-immobility effect of BCP was reverted by pretreatment with inhibitor of catecholamines α-methyl-p-tyrosine (100 mg/kg, i.p.), α-adrenergic antagonist yohimbine (1 mg/kg, i.p.), and β-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 the catecholaminergic system, but not of the 5-HT1A serotonergic receptor, in BCP's antidepressive-like activity. Further...
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 17, 2018
The piperazine derivatives correspond to an extensive chemical class of compounds with numerous n... more 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-...
Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search ... more Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters ...
Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases... more Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases. Crude extract (E-HU) was prepared from H. umbellata subterraneous parts and fractionated by liquid-liquid partition, resulting hexane fraction (HF-HU), dichloromethane fraction (DF-HU), ethyl acetate fraction (EAF-HU) and aqueous fraction (AF-HU). The hibalactone (HU-1) was isolated from the DF-HU and its structure was elucidated by (1)H NMR and (13)C NMR Spectroscopy, mass spectrometry and crystallographic x-ray analysis. The formalin-induced nociception was used to evaluate antinociceptive activity; carrageenan-induced edema and pleurisy tests to evaluate anti-inflammatory activity and light-dark box to evaluate anxiolytic-like activity in mice. The acute oral treatments with E-HU (1000mg/kg), DF-HU (150mg/kg), EAF-HU (400mg/kg) and HU-1 (33mg/kg) decreased the licking time in both phases of the formalin test. In the carrageenan-induced inflammation models, the treatment with the same doses of E-HU, DF-HU, EAF-HU and HU-1 reduced the paw edema formation and leukocytes account into pleural cavity. In silico findings suggest that hibalactone present anti-inflammatory activity by interacting with the enzymes 5-lipoxygenase and cyclooxygenase-2. In the light dark box, the treatments with DF-HU, EAF-HU and HU-1 revealed an anxiolytic like effect. Thus, the E-HU and fractions of H. umbellata showed antinociceptive, anti-inflammatory and anxiolytic like activities, as also hibalactone, a possible phytoconstituent responsible for the biological effects of this specie.
This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine comp... more This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-α and IL-1β levels.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Jan 10, 2017
Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This res... more Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This research aimed to design, synthesis and to evaluate the anti-inflammatory and antinociceptive effects of the new compound, which is derived from nimesulide and darbufelone lead compounds. The new dual inhibitor 5-LOX/COX has the possible advantage of gastrointestinal safety. A voltammetric experiment was conducted to observe the drug's antioxidative effect. A formalin test, a hot plate test and carrageenan-induced mechanical hyperalgesia were employed to evaluate the analgesic nature of LQFM-091. To evaluate anti-inflammatory activity, we measured edema, leukocyte count, myeloperoxidase activity and cytokines levels in carrageenan-induced inflammation tests. We elucidated the underlying mechanisms by assessing the interaction the with COXs and LOX enzymes by colorimetric screening assay and molecular docking. The lethal dose (LD50) was estimated using 3T3 Neutral Red Uptake assay. Our r...
Nitric oxide : biology and chemistry, Jan 13, 2017
The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activ... more The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activities. Furthermore, it has low toxicity, indicating that this compound may be considered to be a good prototype for the development of new analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to investigate the potential anti-inflammatory activity of LQFM-021 using a model of carrageenan-induced inflammation as well as the mechanism of action and role of nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.) reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as decreased protein extravasation and myeloperoxidase activity. This dose of LQFM-021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF-α and IL-1β levels in the pleural cavity. Moreover, pre-t...
The increasing cases of depression has made the searches for new drugs and understanding of the u... more The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4(')-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test - OFT, forced swimming test - FST and tail suspension test - TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1-1000mg/kg)...
Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. To obtain hydroalcohol... more Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. To obtain hydroalcoholic dried extract by nebulization and evaluate its antiulcerogenic potential. Plant material and hydroalcoholic extract were processed and analyzed for their physicochemical characteristics. A method using HPLC was validated to quantify coumarin and o-coumaric acid. Hydroalcoholic extract was spray dried and the powder obtained was characterized in terms of its physicochemical parameters and potential for antiulcerogenic activity. The analytical method proved to be selective, linear, precise, accurate, sensitive, and robust. M. laevigata spray dried extract was obtained using colloidal silicon dioxide as adjuvant and was shown to possess 1.83 ± 0.004% coumarin and 0.80 ± 0.012% o-coumaric acid. It showed significant antiulcer activity in a model of an indomethacin-induced gastric lesion in mice and also produced a gastroprotective effect. This dried extract from M. laevigata could be a pr...
Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usua... more Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usually applied topically on skin, mucous membranes, mouth, and throat, or used for vaginal washings. To analyze the chemical composition of the essential oil from L. sidoides collected in São Gonçalo do Abaeté, Minas Gerais and grown in Hidrolândia, Goiás; to evaluate the antimicrobial activity of the essential oil, crude ethanol extract, and hexane, dichloromethane, ethyl-acetate, and aqueous fractions (AFs); to study the antinociceptive, anti-inflammatory, and central nervous system activities of the crude ethanol extract. The essential oils were obtained by hydro-distillation using a Clevenger-type apparatus and analyzed by GC/MS. The antimicrobial activity in vitro was performed by broth microdilution method. The pharmacological tests were performed using female Swiss albino mice. The major components of the essential oil were isoborneol (14.66%), bornyl acetate (11.86%), α-humulene (11...
The molecular modification and synthesis of compounds is vital to discovering drugs with desirabl... more The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorphenyl)-1H-pyrazol-4-yl]-2H-tetrazole (FPPT). During the acetic acid-induced abdominal writhing test, treatments with FPPT reduced abdominal writhing, while during the formalin test, FPPT reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. FPPT also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, FPPT exhibits a vasorelaxant effect attenuated by Nω-nitro-L-arginine methyl ester, 1H-[1,2, 4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. FPPT also blocked CaCl2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, FPPT reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2,000 mg/kg. Lastly, the…
Low quality of life and life-threatening conditions often demand pharmacological screening of lea... more Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.
Introducao e objetivos: Hydrocotyle umbellata L. Araliaceae (acaricoba) e planta utilizada na med... more Introducao e objetivos: Hydrocotyle umbellata L. Araliaceae (acaricoba) e planta utilizada na medicina popular brasileira por suas propriedades ansioliticas1. Este trabalho investigou o efeito tipo ansiolitico do extrato etanolico das partes subterrâneas de H. umbellata (E-HU) e das fracoes. Metodologia: O extrato e as fracoes foram obtidos conforme metodologia adaptada de Ferri, 19962. Foram utilizados camundongos Swiss machos adultos nos testes do labirinto em cruz elevado (LCE), sono induzido por pentobarbital, caixa claro escuro (CCE) e campo aberto. Resultados e discussoes: E-HU (1g/kg v.o.) demonstrou efeito tipo ansiolitico evidenciado pelo maior percentual de entradas (58,17 3,46%) e maior tempo gasto nos bracos abertos 155,8 12,16 s, no LCE em comparacao ao grupo controle (CTL = veiculo 10 mL/kg v.o.) 44,38 2,82% e 117,4 12,84 s, e um efeito sedativo representado pelo aumento na duracao do sono induzido por pentobarbital (E-HU: 87,70 5,94; CTL: 61,70 4,26 min). A...
Introdução e objetivos: Os compostos pirazolínicos são conhecidos por apresentar atividade anti-i... more Introdução e objetivos: Os compostos pirazolínicos são conhecidos por apresentar atividade anti-inflamatória, analgésica e antipirética. O objetivo deste trabalho foi avaliar o derivado pirazolínico LQFM 021, em testes nociceptivos crônicos de artrite induzida por CFA. Metodologia: Grupos de ratas (n=7) pré-sensibilizados foram tratados (v.o.) com veículo (10 mL/kg 1 vez/dia), LQFM 021 (15 mg/kg 2 vezes/dia) ou LQFM 021 (30 mg/kg 1 vez/dia). Uma hora após os tratamentos foi feito uma injeção intra-articular de CFA. Medidas do tempo de elevação da pata (TEP) e do diâmetro articular foram realizadas até o 6° dia. Resultados e discussões: Tratamento com LQFM 021 30 mg/kg 1 vez/dia promoveu uma redução progressiva e permanente do TEP a partir do 2° dia, em 26,3; 31,4; 31,3; 41,8 e 47,0 %. A formação do edema foi reduzida a partir do 1° dia de tratamento em 29,6; 15,6; 21,2; 29,2 e 29,5 %. Na migração celular, houve uma redução do número de leucócitos em 34,2 % e polimorfonucleares em 54...
Bioassay-guided fractionation of the ethanolic extract of Pterodon emarginatus Vogel stem bark (E... more 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.
The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAla... more The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAlafia multiflora Stapf(AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol aβ-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce signific...
The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAla... more The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAlafia multiflora Stapf(AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol aβ-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce signific...
CNS & neurological disorders drug targets, Jan 20, 2018
This study was conducted to evaluate the antidepressant-like activity of sesquiterpene compound β... more This study was conducted to evaluate the antidepressant-like activity of sesquiterpene compound β-caryophyllene (BCP) for the possible contribution of the monoamine and hippocampal levels of brain-derived neurotrophic factor (BDNF). 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. The anti-immobility effect of BCP was reverted by pretreatment with inhibitor of catecholamines α-methyl-p-tyrosine (100 mg/kg, i.p.), α-adrenergic antagonist yohimbine (1 mg/kg, i.p.), and β-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 the catecholaminergic system, but not of the 5-HT1A serotonergic receptor, in BCP's antidepressive-like activity. Further...
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 17, 2018
The piperazine derivatives correspond to an extensive chemical class of compounds with numerous n... more 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-...
Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search ... more Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters ...
Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases... more Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases. Crude extract (E-HU) was prepared from H. umbellata subterraneous parts and fractionated by liquid-liquid partition, resulting hexane fraction (HF-HU), dichloromethane fraction (DF-HU), ethyl acetate fraction (EAF-HU) and aqueous fraction (AF-HU). The hibalactone (HU-1) was isolated from the DF-HU and its structure was elucidated by (1)H NMR and (13)C NMR Spectroscopy, mass spectrometry and crystallographic x-ray analysis. The formalin-induced nociception was used to evaluate antinociceptive activity; carrageenan-induced edema and pleurisy tests to evaluate anti-inflammatory activity and light-dark box to evaluate anxiolytic-like activity in mice. The acute oral treatments with E-HU (1000mg/kg), DF-HU (150mg/kg), EAF-HU (400mg/kg) and HU-1 (33mg/kg) decreased the licking time in both phases of the formalin test. In the carrageenan-induced inflammation models, the treatment with the same doses of E-HU, DF-HU, EAF-HU and HU-1 reduced the paw edema formation and leukocytes account into pleural cavity. In silico findings suggest that hibalactone present anti-inflammatory activity by interacting with the enzymes 5-lipoxygenase and cyclooxygenase-2. In the light dark box, the treatments with DF-HU, EAF-HU and HU-1 revealed an anxiolytic like effect. Thus, the E-HU and fractions of H. umbellata showed antinociceptive, anti-inflammatory and anxiolytic like activities, as also hibalactone, a possible phytoconstituent responsible for the biological effects of this specie.
This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine comp... more This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-α and IL-1β levels.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Jan 10, 2017
Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This res... more Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This research aimed to design, synthesis and to evaluate the anti-inflammatory and antinociceptive effects of the new compound, which is derived from nimesulide and darbufelone lead compounds. The new dual inhibitor 5-LOX/COX has the possible advantage of gastrointestinal safety. A voltammetric experiment was conducted to observe the drug's antioxidative effect. A formalin test, a hot plate test and carrageenan-induced mechanical hyperalgesia were employed to evaluate the analgesic nature of LQFM-091. To evaluate anti-inflammatory activity, we measured edema, leukocyte count, myeloperoxidase activity and cytokines levels in carrageenan-induced inflammation tests. We elucidated the underlying mechanisms by assessing the interaction the with COXs and LOX enzymes by colorimetric screening assay and molecular docking. The lethal dose (LD50) was estimated using 3T3 Neutral Red Uptake assay. Our r...
Nitric oxide : biology and chemistry, Jan 13, 2017
The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activ... more The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activities. Furthermore, it has low toxicity, indicating that this compound may be considered to be a good prototype for the development of new analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to investigate the potential anti-inflammatory activity of LQFM-021 using a model of carrageenan-induced inflammation as well as the mechanism of action and role of nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.) reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as decreased protein extravasation and myeloperoxidase activity. This dose of LQFM-021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF-α and IL-1β levels in the pleural cavity. Moreover, pre-t...
The increasing cases of depression has made the searches for new drugs and understanding of the u... more The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4(')-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test - OFT, forced swimming test - FST and tail suspension test - TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1-1000mg/kg)...
Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. To obtain hydroalcohol... more Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. To obtain hydroalcoholic dried extract by nebulization and evaluate its antiulcerogenic potential. Plant material and hydroalcoholic extract were processed and analyzed for their physicochemical characteristics. A method using HPLC was validated to quantify coumarin and o-coumaric acid. Hydroalcoholic extract was spray dried and the powder obtained was characterized in terms of its physicochemical parameters and potential for antiulcerogenic activity. The analytical method proved to be selective, linear, precise, accurate, sensitive, and robust. M. laevigata spray dried extract was obtained using colloidal silicon dioxide as adjuvant and was shown to possess 1.83 ± 0.004% coumarin and 0.80 ± 0.012% o-coumaric acid. It showed significant antiulcer activity in a model of an indomethacin-induced gastric lesion in mice and also produced a gastroprotective effect. This dried extract from M. laevigata could be a pr...
Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usua... more Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as an antiseptic, and it is usually applied topically on skin, mucous membranes, mouth, and throat, or used for vaginal washings. To analyze the chemical composition of the essential oil from L. sidoides collected in São Gonçalo do Abaeté, Minas Gerais and grown in Hidrolândia, Goiás; to evaluate the antimicrobial activity of the essential oil, crude ethanol extract, and hexane, dichloromethane, ethyl-acetate, and aqueous fractions (AFs); to study the antinociceptive, anti-inflammatory, and central nervous system activities of the crude ethanol extract. The essential oils were obtained by hydro-distillation using a Clevenger-type apparatus and analyzed by GC/MS. The antimicrobial activity in vitro was performed by broth microdilution method. The pharmacological tests were performed using female Swiss albino mice. The major components of the essential oil were isoborneol (14.66%), bornyl acetate (11.86%), α-humulene (11...
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