Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 40(9): 5015-5024, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878789

RESUMO

BACKGROUND/AIM: Despite being a rare disease, melanoma is considered the most dangerous skin cancer due to its highly invasive and aggressive nature, and still requires for more effective treatments. The aim of this study was to evaluate the in vitro anti-melanoma potential of Ephedranthus pisocarpus R.E.Fr. (Annonaceae), a popular Brazilian plant with medicinal properties. MATERIALS AND METHODS: Initially, the ethanolic extract (EtOH) was obtained from E. pisocarpus leaves and later partitioned using increasing polarity solvents. The anti-melanoma potential of E. pisocarpus was assessed by spectrophotometry and its cytotoxicity determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. RESULTS: We demonstrated that the EtOH extract and fractions from E. pisocarpus had a moderate photoprotective action (FPS 3.0-5.0) against UVA radiation. Interestingly, the dichloromethane fraction presented higher anti-melanoma activity against B16-F10 (IC50=46.8 µg/ml) and SK-MEL-28 cells (IC50=40.1 µg/ml) and lesser toxicity on normal cells. Additionally, our study reported that spathulenol, one of the major constituents from E. pisocarpus, acts through an apoptosis-dependent mechanism in SK-MEL-28 cells. CONCLUSION: The present study demonstrated, for the first time, the in vitro anti-melanoma potential of E. pisocarpus against melanoma cells.


Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Brasil , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxicidade Imunológica , Relação Dose-Resposta a Droga , Hemólise , Humanos , Melanoma Experimental , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
2.
Anticancer Res ; 40(9): 5049-5057, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878793

RESUMO

BACKGROUND/AIM: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. MATERIALS AND METHODS: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. RESULTS: AMTAC-06 did not induce toxicity on zebrafish and mice (LD50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1ß and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. CONCLUSION: AMTAC-06 has low toxicity and a significant antitumor activity.


Assuntos
Acridinas/farmacologia , Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Fatores Imunológicos/farmacologia , Compostos de Espiro/farmacologia , Acridinas/química , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Camundongos , Estrutura Molecular , Compostos de Espiro/química , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
3.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32928735

RESUMO

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.

4.
Biomed Pharmacother ; 109: 1394-1405, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551390

RESUMO

Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies due to cancer treatment. Among the antioxidants consumed, there are vitamins, including retinyl palmitate (PR) and ascorbic acid (AA), which have the capacity to reduce free radicals formation, protect cellular structures and maintain the cellular homeostasis. This systematic review evaluated the antioxidant and antitumor mechanisms of retinol palmitate (a derivative of vitamin A) and/or ascorbic acid (vitamin C) in cancer-related studies. Ninety-seven (97) indexed articles in the databases PubMed and Science Direct, published between 2013 and 2017, including 23 clinical studies (5 for every single compound while 13 in interaction) and 74 non-clinical studies (37 for retinol palmitate, 36 for ascorbic acid and 1 in interaction) were considered. Antioxidant and antitumor effects, with controversies over dosage and route of administration, were observed for the test compounds in their isolated form or associated in clinical studies. Prevention of cancer risks against oxidative damage was seen in lower doses of retinol palmitate and/or vitamin C. However, at high doses, they can generate reactive oxygen species, cytotoxicity and apoptosis in test systems. Non-clinical studies using cell lines have allowed understanding the mechanisms related to antioxidants and antitumor effects of the isolated compounds, however, studies on vitamin interactions, acting as antioxidants and/or antitumor are still rare and controversial. More studies, mainly related to modulation of antineoplastic drugs are needed for understanding the risks and benefits of their use during treatment in order to achieve effectiveness in cancer therapy and patient's quality of life.


Assuntos
Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Vitamina A/análogos & derivados , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Diterpenos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Vitamina A/farmacologia , Vitamina A/uso terapêutico
5.
Naunyn Schmiedebergs Arch Pharmacol ; 390(9): 893-903, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28643086

RESUMO

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Ácido Elágico/farmacologia , Ácido Gálico/farmacologia , Leishmaniose Cutânea/tratamento farmacológico , Animais , Antiprotozoários/administração & dosagem , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Ácido Elágico/administração & dosagem , Feminino , Ácido Gálico/administração & dosagem , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Leishmania major/efeitos dos fármacos , Leishmania major/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
6.
Pharm Biol ; 55(1): 782-786, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28103733

RESUMO

CONTEXT: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties. OBJECTIVE: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify and quantify the constituents of the T. capitatus EO. The antinociceptive activity was evaluated in vivo by the glutamate-induced nociception model in male Swiss mice (25 g), at doses of 3, 6 and 12 mg/kg, 1 h before evaluation of the licking time response (0-15 min). The mechanism of T. capitatus EO (1-500 µg/mL) on the isolated nerve excitability of Wistar rat (300 g) was assessed by the single sucrose technique. RESULTS AND DISCUSSION: The EO of T. capitatus presented 33 components, mainly monoterpenes and sesquiterpenes, carvacrol (ca. 80%) was its major constituent. T. capitatus EO induced antinociception in orally treated mice (3, 6, and 12 mg/kg) reducing the licking time from control (100.3 ± 11.9 s) to 84.8 ± 12.2, 62.7.6 ± 9.9, and 41.5 ± 12.7 s, respectively (n = 8; p < 0.05). Additionally, we have demonstrated that T. capitatus EO (500 µg/mL) decreased the compound action potential amplitude (VCAP) of about 80.0 ± 4.3% from control recordings (n = 4; p < 0.05). Such activity was presumably mediated through a voltage-gated Na+ channels. CONCLUSIONS: The present study demonstrated the antinociceptive activity of Thymus capitatus essential oil, which acts via peripheral nervous excitability blockade.


Assuntos
Analgésicos/análise , Óleos Voláteis/análise , Óleos Vegetais/análise , Thymus (Planta) , Analgésicos/farmacologia , Animais , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Camundongos , Óleos Voláteis/farmacologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Óleos Vegetais/farmacologia , Ratos , Ratos Wistar
7.
J Ethnopharmacol ; 124(3): 440-3, 2009 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-19505550

RESUMO

AIM OF THE STUDY: Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. MATERIALS AND METHODS: Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. RESULTS: The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. CONCLUSIONS: From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Hipnóticos e Sedativos , Lauraceae/química , Óleos Vegetais/farmacologia , Monoterpenos Acíclicos , Animais , Comportamento Animal/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Camundongos , Monoterpenos/química , Monoterpenos/farmacologia , Condução Nervosa/efeitos dos fármacos , Pentobarbital/farmacologia , Óleos Vegetais/análise , Ratos , Ratos Wistar , Sono/efeitos dos fármacos , Sacarose
8.
Biol Pharm Bull ; 31(5): 1017-20, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18451538

RESUMO

(-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.


Assuntos
Analgésicos , Monoterpenos/farmacologia , Nervos Periféricos/efeitos dos fármacos , Acetatos , Potenciais de Ação/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Animais , Monoterpenos Cicloexânicos , Diazepam/farmacologia , Eletrofisiologia , Formaldeído , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Monoterpenos/antagonistas & inibidores , Monoterpenos/química , Morfina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , Estereoisomerismo , Sacarose
9.
Neurosci Lett ; 401(3): 231-5, 2006 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-16650577

RESUMO

Citronellol is one monoterpene alcohol, which is present in the essential oils of various aromatic plant species. This study evaluated the neuroprotective activity of citronellol on pentylenetetrazol- and picrotoxin-induced convulsions and maximal electroshock-induced seizures in mice. Administration of citronellol significantly reduced the number of animals of convulsion induced by pentylenetetrazol and eliminated the extensor reflex of maximal electroshock-induced seizures test in about 80% of the experimental animals. In addition, administration of citronellol showed protection in the pentylenetetrazol and picrotoxin tests by increasing the latency of clonic seizures. We also investigated the effect of citronellol in the rat isolated nerve using the single sucrose-gap technique. We showed that the amplitude of the compound action potential decreased more than 90% when the monoterpene was incubated for 30 min at 6.4 mM and we did not verify any effect on the repolarization of the compound action potential. Taken together, our results demonstrated an anticonvulsant activity of the citronellol that could be, at least in part, explained by the diminution of the action potential amplitude.


Assuntos
Anticonvulsivantes/uso terapêutico , Monoterpenos/uso terapêutico , Convulsões/tratamento farmacológico , Potenciais de Ação/efeitos dos fármacos , Monoterpenos Acíclicos , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletrochoque/efeitos adversos , Masculino , Camundongos , Condução Nervosa/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Picrotoxina/toxicidade , Tempo de Reação/efeitos dos fármacos , Convulsões/etiologia , Convulsões/fisiopatologia , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...