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1.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-37259336

RESUMEN

Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. ß-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of ß-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. ß-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 µM) and axenic amastigotes (EC50 = 1.12 µM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. ß-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 µM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that ß-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.

2.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38276002

RESUMEN

Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic-lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund's adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1ß levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose-response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration.

3.
Pharmaceutics ; 14(12)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36559198

RESUMEN

Isopropyl gallate (IPG) is a polyphenol obtained from alterations in the gallic acid molecule via acid catalysis with previously reported leishmanicidal and trypanocidal activities. The present study aims to evaluate in silico binding activity towards some targets for antileishmanial chemotherapy against Leishmania major species, and ADMET parameters for IPG, as well as in vitro antileishmanial and cytotoxic effects. Molecular docking was performed using AutoDockVina and BIOVIA Discovery Studio software, whereas in silico analysis used SwissADME, PreADMET and admetSAR software. In vitro antileishmanial activity on promastigotes and amastigotes of Leishmania major, cytotoxicity and macrophages activation were assessed. IPG exhibited affinity for pteridine reductase (PTR1; -8.2 kcal/mol) and oligopeptidase B (OPB; -8.0 kcal/mol) enzymes. ADMET assays demonstrated good lipophilicity, oral bioavailability, and skin permeability, as well as non-mutagenic, non-carcinogenic properties and low risk of cardiac toxicity for IPG. Moreover, IPG inhibited the in vitro growth of promastigotes (IC50 = 90.813 µM), presented significant activity against amastigotes (IC50 = 13.45 µM), promoted low cytotoxicity in macrophages (CC50 = 1260 µM), and increased phagocytic capacity. These results suggest IPG is more selectively toxic to the parasite than to mammalian cells. IPG demonstrated acceptable in silico pharmacokinetics parameters, and reduced infection and infectivity in parasitized macrophages, possibly involving macrophage activation pathways and inhibition of leishmania enzymes.

4.
Molecules ; 25(23)2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33255253

RESUMEN

Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs to treat a wide array of pathologies. Some alkaloids have antiviral activity and/or have been used as prototypes in the development of synthetic antiviral drugs. In this study, eleven anti-coronavirus alkaloids were identified from the scientific literature and their potential therapeutic value against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is discussed. In this study, in silico studies showed an affinity of the alkaloids for binding to the receptor-binding domain of the SARS-CoV-2 spike protein, putatively preventing it from binding to the host cell. Lastly, several mechanisms for the known anti-coronavirus activity of alkaloids were discussed, showing that the alkaloids are interesting compounds with potential use as bioactive agents against SARS-CoV-2.


Asunto(s)
Alcaloides/química , Antivirales/química , Tratamiento Farmacológico de COVID-19 , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Alcaloides/uso terapéutico , Antivirales/uso terapéutico , COVID-19/virología , Humanos , Pandemias , SARS-CoV-2/química , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/química
5.
Biomolecules ; 11(1)2020 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-33374457

RESUMEN

Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.


Asunto(s)
Antivirales/uso terapéutico , Dengue/tratamiento farmacológico , Fenoles/uso terapéutico , Replicación Viral/efectos de los fármacos , Animales , Chlorocebus aethiops , Dengue/genética , Dengue/patología , Dengue/virología , Virus del Dengue/efectos de los fármacos , Virus del Dengue/genética , Virus del Dengue/patogenicidad , Humanos , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Células Vero/efectos de los fármacos , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/genética
6.
Molecules ; 25(23)2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33297540

RESUMEN

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , COVID-19/complicaciones , Quercetina/farmacología , Lesión Renal Aguda/etiología , Animales , COVID-19/epidemiología , Humanos , Morbilidad , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Quercetina/uso terapéutico , Tratamiento Farmacológico de COVID-19
7.
Molecules ; 25(19)2020 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-33036315

RESUMEN

Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of Trypanosoma.


Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Aceites Volátiles/uso terapéutico , Animales , Humanos , Extractos Vegetales/uso terapéutico , Tripanocidas/uso terapéutico , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma brucei brucei/patogenicidad , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/patogenicidad , Tripanosomiasis Africana/tratamiento farmacológico
8.
Molecules ; 24(24)2019 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-31817569

RESUMEN

Depression is a health problem that compromises the quality of life of the world's population. It has different levels of severity and a symptomatic profile that affects social life and performance in work activities, as well as a high number of deaths in certain age groups. In the search for new therapeutic options for the treatment of this behavioral disorder, the present review describes studies on antidepressant activity of cinnamic acids, which are natural products found in medicinal plants and foods. The description of the animal models used and the mechanisms of action of these compounds are discussed.


Asunto(s)
Antidepresivos/uso terapéutico , Cinamatos/uso terapéutico , Depresión/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Desarrollo de Medicamentos
9.
Molecules ; 24(13)2019 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-31261921

RESUMEN

Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.


Asunto(s)
Acrilamidas/química , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Piperidonas/síntesis química , Piperidonas/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dioxolanos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Simulación del Acoplamiento Molecular , Piperidonas/química
10.
Braz. J. Pharm. Sci. (Online) ; 53(4): e00076, 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-889414

RESUMEN

ABSTRACT Considering the reported activity of carvone in the literature, this study aimed to evaluate the antimicrobial, cytotoxic and chemopreventive activities of (+)- and (-)-carvone, (+)- and (-)- hydroxydihydrocarvone and α,ß-epoxycarvone. (+)-Hydroxydihydrocarvone (HC+), (-)-hydroxydihydrocarvone (HC-) and α,ß-epoxycarvone (EP) were obtained by synthesis using (+)-carvone (C+) or (-)-carvone (C-) as precursors. The antifungal activity (MIC and MFC) were evaluated against Candida parapsilosis, C. tropicalis, C. krusei and C. albicans and the antibacterial activity (MIC and MBC) against Escherichia coli and Staphylococcus aureus. The cytotoxicity assays were performed with human cancer cell lines HepG-2 and SiHa and the normal strain MRC-5 through sulphorrodamine B assay. Chemoprevention was evaluated through quinone reductase assay. Our results showed no cytotoxicity on tumor and normal cell lines and no induction of the quinone reductase enzyme. C- and HC- presented activity against E. coli. All compounds presented weak antifungal activity against C. tropicalis and C. parapsilosis. EP and C+ showed moderate activity against C. krusei. Results suggest the potential use of carvones and its derivatives as antifungal agents against Candida yeasts. The absence of cytotoxicity in cell lines indicates safety in the use of these compounds


Asunto(s)
Aceites Volátiles/análisis , Quimioprevención , Carum/clasificación , Antiinfecciosos/análisis , Quimioprevención , Antifúngicos
11.
Molecules ; 21(12)2016 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-27983602

RESUMEN

A collection of 32 structurally related N-(4-halobenzyl)amides were synthesized from cinnamic and benzoic acids through coupling reactions with 4-halobenzylamines, using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling agent. The compounds were identified by spectroscopic methods such as infrared, ¹H- and 13C- Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry. The compounds were then submitted to antimicrobial tests by the minimum inhibitory concentration method (MIC) and nystatin was used as a control in the antifungal assays. The purpose of the tests was to evaluate the influence of structural changes in the cinnamic and benzoic acid substructures on the inhibitory activity against strains of Candida albicans, Candida tropicalis, and Candida krusei. A quantitative structure-activity relationship (QSAR) study with KNIME v. 3.1.0 and Volsurf v. 1.0.7 softwares were realized, showing that descriptors DRDRDR, DRDRAC, L4LgS, IW4 and DD2 influence the antifungal activity of the haloamides. In general, 10 benzamides revealed fungal sensitivity, especially a vanillic amide which enjoyed the lowest MIC. The results demonstrate that a hydroxyl group in the para position, and a methoxyl at the meta position enhance antifungal activity for the amide skeletal structure. In addition, the double bond as a spacer group appears to be important for the activity of amide structures.


Asunto(s)
Amidas/síntesis química , Antifúngicos/síntesis química , Antifúngicos/farmacología , Amidas/farmacología , Candida/efectos de los fármacos , Espectroscopía de Resonancia Magnética con Carbono-13 , Simulación por Computador , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Espectroscopía de Protones por Resonancia Magnética , Relación Estructura-Actividad Cuantitativa
12.
Artículo en Portugués | LILACS | ID: lil-672227

RESUMEN

The antioxidant potential of nerolidol against the formation of thiobarbituric acid reactive substances (TBARS), hydroxyl radical and nitric oxide production was assessed in this study. At concentrations of 0.9, 1.8, 3.6, 5.4 and 7.2 mg/mL, it was observed that nerolidol prevented lipid peroxidation induced by 2,2?-azobis-2-amidinopropane (AAPH), inhibiting the formation of TBARS in a manner similar to that of Trolox, a synthetic hydrophilic ?-tocopherol analog that is widely used as an antioxidant standard. Nerolidol also reduced the production of the hydroxyl radical and nitric oxide, possibly indicating an in-vitro antioxidant property. This property could be exploited to protect in-vivo molecular targets (DNA, lipids, carbohydrates and proteins). Although nerolidol exhibited in-vitro antioxidant activity, by its capacity to remove hydroxyl radicals and nitric oxide and to prevent the formation of TBARS, more research is needed to characterize better the antioxidant potential of this compound.


O presente estudo avaliou o potencial antioxidante do nerolidol contra a formação de substâncias reativas ao ácido tiobarbitúrico (TBARS), radical hidroxila e produção de óxido nítrico. Nas concentrações de 0,9, 1,8, 3,6, 5,4 e 7,2 ?g/mL foi observado que o nerolidol preveniu a peroxidação lipídica induzida por 2,2?-azobis-2-amidinopropano(AAPH), inibindo a quantidade de TBARS formado, de maneira semelhante ao composto Trolox, um análogo sintético hidrofílico do ?-tocoferol, que é muito utilizado como padrão antioxidante. Além disso, o nerolidol também reduziu a produção do radical hidroxila, assim como a produção de óxido nítrico, possivelmente devido a uma propriedade antioxidante in vitro, que pode ser explorada para a proteção in vivo de alvos moleculares (DNA, lipídios, carboidratos e proteínas). O nerolidol apresentou potencial antioxidante in vitro, por meio da capacidade de remoção de radicais hidroxilas e do óxido nítrico, bem como na prevenção da formação de TBARS. No entanto, mais estudos são necessários para caracterizar melhor o potencial antioxidante in vitro deste composto


Asunto(s)
Antioxidantes , Radical Hidroxilo , Peroxidación de Lípido , Óxido Nítrico
13.
Artículo en Portugués | LILACS | ID: lil-667057

RESUMEN

O presente estudo avaliou o potencial antioxidante in vitro da ciano-carvona contra a formação de substâncias reativas com o ácido tiobarbitúrico (TBARS), radical hidroxila e produção de óxido nítrico. Observou-se que a ciano-carvona (0,9, 1,8, 3,6, 5,4 e 7,2 μg/mL), foi capaz de prevenir a peroxidação lipídica induzida por 2,2'-azobis-2-amidinopropano (AAPH), inibindo a quantidade de TBARS formada. Resultado semelhante foi obtido com o Trolox (140 μg/mL), um análogo sintético hidrofílico do α-tocoferol, que é largamente usado como padrão antioxidante. Este resultado sugere que a ciano-carvona pode exercer um efeito antioxidante contra a peroxidação lipídica in vivo. A ciano-carvona também produziu uma remoção do radical hidroxila, sugerindo uma possível capacidade de proteção contra danos celulares in vitro produzidos por este radical. O Trolox também reduziu significativamente a quantidade deste radical. Em relação à produção de óxido nítrico, foi detectado uma diminuição significativa na produção deste composto pela ciano-carvona, demonstrando uma propriedade antioxidante in vitro, um achado que pode ser explorado para a proteção in vivo das biomoléculas, como lipídios da membrana celular. A ciano-carvona revelou potencial antioxidante in vitro, por meio da capacidade de remoção contra radicais hidroxilas e do óxido nítrico, bem como preveniu a formação de TBARS.


The in vitro antioxidant potential of the monoterpene cyano-carvone was tested against the formation of thiobarbituric acid reactive substances (TBARS) and production of hydroxyl radical and nitric oxide. It was observed that cyano-carvone (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL) was capable of reducing lipid peroxidation induced by 2,2'-azobis-2-amidinopropane (AAPH), thus inhibiting TBARS generation. Similar results were obtained with Trolox (140 μg/mL), a synthetic analogue of the hydrophilic α-tocopherol, which is widely used as an antioxidant standard. This result suggests that cyano-carvone may exert an antioxidant effect against lipid peroxidation in vivo. Cyano-carvone also led to removal of the hydroxyl radical, indicating a potential ability to protect against in vitro cell damage produced by this radical. Trolox also reduced significantly the amount of this radical. Regarding nitric oxide production, this was significantly lowered by cyano-carvone, demonstrating an antioxidant property in vitro, which could be exploited in vivo to protect biomolecules such as lipids of the cell membrane. In sum, cyano-carvone showed an in vitro antioxidant potential, by its capacity to remove hydroxyl radicals and nitric oxide, and prevented TBARS formation.


Asunto(s)
Antioxidantes , Radical Hidroxilo , Peroxidación de Lípido , Monoterpenos , Óxido Nítrico , Aceites Volátiles
14.
Artículo en Portugués | LILACS | ID: lil-658501

RESUMEN

O fitol, (3,7,11,15-tetrametilhexadec-2-en-1-ol), é um diterpeno pertencente ao grupo dos álcoois acíclicos insaturados de cadeia longa e ramificada. É um componente da molécula da clorofila, presente em folhas verdes de várias plantas medicinais. Entretanto, pouco é descrito na literatura sobre os possíveis efeitos toxicológicos produzidos pelo fitol. O objetivo do nosso estudo foi avaliar a toxicidade aguda do fitol, após administração intraperitoneal para determinação da dose letal 50% (DL50) e os efeitos sobre os parâmetros bioquímicos, hematológicos e histopatológicos no hipocampo e corpo estriado de camundongos adultos tratados com fitol nas doses de 25, 50 e 75 mg/kg. Os testes para determinação do grau de toxicidade aguda, bem como a investigação da DL50, revelou que o valor é aproximadamente 1153.39 mg/kg. Os camundongos tratados com as doses selecionadas do fitol a partir da DL50 apresentaram todos os parâmetros hematológicos dentro da faixa de referência, observando-se alterações nos valores dos linfócitos. Por sua vez, a maioria dos valores dos parâmetros bioquímicos diminuiu em todas as doses testadas (p<0,05). Em nosso estudo, apenas os animais tratados com fitol na dose de 75 mg/kg demonstraram uma discreta vacuolização no corpo estriado e um discreto comprometimento caracterizado por vacuolização no hipocampo em apenas um dos animais. Nossos resultados indicam que o tratamento com fitol não produz alterações hematológicas, bioquímicas e histopatológicas cerebrais em camundongos. O estudo toxicológico pré-clínico com fitol demonstrou que o produto avaliado possui discreta toxicidade aguda por via intraperitoneal, sendo estes dados uma contribuição para pesquisas com compostos obtidos de plantas medicinais com potencial farmacológico. Porém, ressalta-se a necessidade de futuras pesquisas que possibilitem comparar os resultados em outras vias, bem como para realizar análises anatomopatológicas dos animais tratados com fitol, para assegurar o uso seguro deste diterpeno.


Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol) is a diterpene belonging to the group of acyclic unsaturated long-chain branched alcohols. It is a component of the chlorophyll molecule, present in green leaves of various medicinal plants. However, there is little in the literature about the possible toxic effects produced by phytol. The aim of our study was to assess the acute toxicity of phytol after intraperitoneal (ip) administration, by determining its 50% lethal dose (LD50) and effects on biochemical parameters, hematology and the histopathology of the hippocampus and corpus striatum of adult mice treated with doses of 25, 50 and 75 mg/kg phytol. The acute toxicity tests and investigation of the LD50 revealed its value to be approximately 1153.39 mg/kg. Mice treated with sublethal doses of phytol based on the LD50 showed all hematological parameters within their reference ranges, with small changes in the lymphocyte count. In turn, most of the biochemical parameters decreased at all doses tested (p<0.05). In our study, only those animals treated with phytol at a dose of 75 mg/kg showed slight vacuolation in the corpus striatum and a slight impairment characterized by vacuolation in the hippocampus in one animal. Our results indicate that treatment with phytol produces no hematological, biochemical or brain histopathological changes in the mice. The preclinical toxicological study with phytol showed that it has slight acute toxicity when injected ip. These data contribute to research on natural compounds obtained from medicinal plants with pharmacological potential. However, we emphasize the need for future research to enable results obtained by other routes to be compared, as well as to conduct pathological analysis in animals treated with phytol, to ensure the safe use of this diterpene.


Asunto(s)
Animales , Masculino , Ratones , Fitol/toxicidad , Ratones
15.
Rev. bras. ciênc. saúde ; 16(03)out. 2012.
Artículo en Portugués | LILACS | ID: lil-655237

RESUMEN

Objetivo: Avaliar a segurança da ciano-carvona por meio de estudos de toxicidade aguda e o seu potencial ansiolítico. Material e Métodos: Camundongos Swiss machos foram tratados com ciano-carvona (v.o) em doses crescentes de 25 a 2000 mg/kg e observados durante 14 dias em relação às alterações comportamentais e taxa de mortalidade. Posteriormente foram realizados exames hematológicos, bioquímicos e análise macroscópica dos principais órgãos. Além disso, outros grupos de animais foram tratados com as doses de 25, 50 e 75 mg/kg, para avaliação da atividade locomotora, do efeito ansiolítico e da coordenação motora. Resultados: No teste hipocrático, devido à ausência de mortalidade, a DL50 não foi determinada. Os sinais clínicos foram discretos, reversíveis e observados apenas nas maiores doses. Dessa forma, em relação às análises hematológicas e bioquímicas não foram verificadas alterações significativas. Nos estudos comportamentais verificou-se uma redução da atividade locomotora, um maior número de entradas nos braços abertos, bem como um maior tempo de permanência nos braços abertos, sugerindo um possível efeito ansiolítico. Em relação ao teste do rota rod não foi verificada alteração no tempo de permanência na barra giratória, bem como não foi detectado mudanças no número de quedas. Conclusão: Este estudo demonstrou que a ciano-carvona não apresenta toxicidade aguda, sugerindo um efeito ansiolítico que precisa ser melhor investigado para a elucidação do seu mecanismo de ação.


Objective: To evaluate the safety of cyano-carvone by means of acute toxicity studies and to investigate its anxiolytic potential. Material and Methods: Swiss male mice were treated with cyano-carvone (v.o) in escalating doses from 25 to 2000 mg/kg and observed for 14 days as regards behavioral changes and mortality rate. After this time period, hematological, biochemical and morphological analyses of the main macroscopic organs were carried out. In addition, other groups of animals were treated with doses of 25, 50 and 75 mg/kg in order to assess locomotor activity, anxiolytic effect and motor coordination. Results: In the Hippocratic test, the compound did not cause any deaths among the mice, thus the LD50 was not determined and clinical signs that emerged were discrete, reversible and observed only in higher doses. Accordingly, hematological and biochemical analyses did not show significant alterations. In the behavioral analysis, it was found a reduction of locomotor activity and a greater number of entries in open arms, as well as a longer time spent with open arms, suggesting an anxiolytic effect. In the Rota-rod test it was observed no change in the permanence time on the spinning rod, as well as no changes were detected for the number of falls. Conclusion: This study demonstrated that cyano-carvone has no acute toxicity, and suggests a possible anxiolytic effect that needs to be further investigated in order to elucidate its mechanism of action.

16.
Eur J Pharm Sci ; 44(4): 455-61, 2011 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-21924353

RESUMEN

This work examined the gastroprotection of (-)-α-bisabolol, an unsaturated optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants. (-)-α-Bisabolol has been described as a compound capable of reducing the gastric ulcer area in response to absolute ethanol. We evaluated the gastroprotection of (-)-α-bisabolol in ethanol-induced gastric lesions model through histopathological assessment, measurement of the membrane lipids peroxidation (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and the nitrite amount. Our results showed that (-)-α-bisabolol was able to reduce injuries associated with the administration of ethanol and the formation of thiobarbituric acid reactive substances (MDA) was also able to increase SOD activity and reduce the influx of cells inflammatory (neutrophils) in the gastric mucosa. The effect of (-)-α-bisabolol seems to be unrelated to the nitric oxide. (-)-α-Bisabolol caused a reduction of catalase activity. These findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Neutrófilos/patología , Sustancias Protectoras/farmacología , Sesquiterpenos/farmacología , Úlcera Gástrica/prevención & control , Superóxido Dismutasa/metabolismo , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Animales , Catalasa/metabolismo , Etanol/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/enzimología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos , Sesquiterpenos Monocíclicos , Neutrófilos/metabolismo , Nitritos/metabolismo , Peroxidasa/metabolismo , Sustancias Protectoras/uso terapéutico , Sesquiterpenos/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología
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