RESUMO
Pterodon pubescens Benth. is widely used in folk medicine for the treatment of inflammatory conditions, with the activity attributed to the compounds with a vouacapan moiety, however, few studies report the toxicological evaluation of the extract and safety issues related to the species. Herein the non-clinical toxicity, in in vivo and in vitro tests, of dichloromethane crude extract of Pterodon pubescens fruits (PPE) and vouacapan diterpene furan isomer´s mixture (1:1) 6α-hydroxy-7ß-acetoxy-vouacapan-17ß-oate methyl ester and 6α-acetoxy-7ß-hydroxy-vouacapan-17ß-oate methyl ester isomers (VDFI mixture) is reported. Toxicological evaluation of 110-day repeated dose oral toxicity study, as hematological, biochemical, and histopathological parameters demonstrated that animals (male and female Wistar rats) treated with PPE presented no signs of toxicity, nevertheless daily high dose administration (500 mg/Kg) altered the metabolic homeostasis of animals that manifested microgoticular hepatic steatosis. Biochemical and histopathological results of animals (female Swiss mice) treated daily with VDFI mixture, at the highest dose (300 mg/Kg), indicated liver toxicity in one animal causing acute hepatotoxicity. Alkaline Comet assay demonstrated that PPE and VDFI mixture increased the percentage of DNA fragmentation without interfering with the tail moment parameter, but only VDFI mixture (30 µg/mL) presented statistical difference. In the micronucleus induction test, PPE and VDFI mixture did not demonstrate mutagenic potential. Our data provide evidence for the safety use of PPE and VDFI mixture in lower doses enabling further clinical studies and the development of herbal medicine.
Assuntos
Fabaceae , Frutas , Animais , Ésteres , Fabaceae/química , Fabaceae/toxicidade , Feminino , Frutas/toxicidade , Masculino , Camundongos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Testes de Toxicidade AgudaRESUMO
Essential oils (EOs) are bioactive compounds with therapeutic potential for use as alternatives or as support to conventional treatments. However, EOs present limitations, such as sensibility to environmental factors, which can be overcome through microencapsulation. The objective of this study was to produce, by spray drying, chitosan microparticles (CMs) loaded with EO of Lemongrass (Cymbopogon flexuosus), Geranium (Pelargonium x ssp) and Copaiba (Copaifera officinalis). Physicochemical and biological characterization of these microparticles showed that CMs presented spherical morphology, had an average size range of 2-3 µm with positive zeta potential (ZP) values, and enhanced thermal stability, compared to free EO. The encapsulation efficiency (EE) ranged from 4.8-58.6%, depending on the oil's properties. In vitro EO release from CMs was determined at different pHs, with 94% release observed in acid media. All microparticles were non-hemolytic at concentrations of up to 0.1 mg·mL-1. EOs and CMs presented acetylcholinesterase (AChE) inhibition activity (IC 50 ranged from 11.92 to 28.18 µg·mL-1). Geranium and Copaiba EOs presented higher toxicity against Artemia salina, and greater inhibition of acetylcholinesterase, indicating potential bioactivity for Alzheimer's disease (AD). Our findings demonstrate that CM systems may show promise for the controlled release of these EOs.
Assuntos
Artemia/efeitos dos fármacos , Cápsulas/química , Quitosana/química , Inibidores da Colinesterase/farmacologia , Cymbopogon/química , Fabaceae/química , Óleos Voláteis/análise , Pelargonium/química , Animais , Sangue/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Cymbopogon/toxicidade , Fabaceae/toxicidade , Hemólise , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Microscopia Eletrônica de Varredura , Óleos Voláteis/química , Tamanho da Partícula , Pelargonium/toxicidade , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The purpose of the survey was to determine acute & chronic toxicity; in vivo antioxidant and anti-inflammatory actions of the different extracts of A. fraxinifolius Wight and Arn bark; along with estimation of the phenolic, flavonoidal contents and investigation of phenolic metabolites that may attribute to the activities. LD50 of the total ethanol extract (TEE) was 7.1 g/kg b. wt, the radical scavenging activity of DPPH showed 60.31% inhibition, FRAP ability and ABTS+ activity showed 55.024 and 67.217 µmol Trolox/100 g dry weight, respectively. TEE followed by ethyl acetate extract (EAE) at 100 mg/kg b.w exhibited the highest in vivo antioxidant activity (94.51% and 91.08% potency, respectively) compared with Vit E (100%). The TEE & EAE exhibited the highest anti-inflammatory activity (3.81±0.08 & 3.79±.0.04) respectively in comparison with indomethacin 3.83±0.01 measured as edema diameter after 4 hours of extract administration. The total phenolic and total flavonoid contents in the total ethanol extract (TEE) estimated as gallic acid and catechin equivalents were 61.06± 0.08 µg eq GA/g, 40.33± 0.20 µg CE/g extract respectively. EAE revealed five phenolic acids and eight flavonoid compounds isolated for the first time from the plant
Assuntos
/análise , Fabaceae/toxicidade , Antioxidantes/análise , Ácidos/efeitos adversos , Etanol , Dose Letal Mediana , Acetatos/administração & dosagemRESUMO
Este trabalho descreve um surto de rumenite e abomasite decorrente de sobrecarga de carboidratos em um rebanho de 238 bezerros, com idades entre 12 e 15 meses, causada pela ingestão dos frutos de Enterolobium contortisiliquum. As taxas de morbidade, mortalidade e letalidade foram de, respectivamente, 12,7%, 5,2% e 42,1%. Clinicamente, os bovinos apresentaram fotossensibilização, salivação e diarreia. Os achados de necropsia foram semelhantes nos dois bezerros necropsiados e consistiram de fotodermatite e rumenite ulcerativa multifocal, subaguda a crônica, e abomasite. A relevância deste relato é que, pela primeira vez, foi possível associar a ocorrência da rumenite devido à sobrecarga de carboidratos com a intoxicação espontânea por E. contortisiliquum em bovinos, confirmando achados anteriormente descritos em experimentos realizados com ovinos.(AU)
Assuntos
Animais , Bovinos , Intoxicação por Plantas/veterinária , Rúmen/patologia , Acidose/veterinária , Abomaso/patologia , Transtornos de Fotossensibilidade/veterinária , Plantas Tóxicas , Fabaceae/toxicidadeRESUMO
Este trabalho descreve um surto de rumenite e abomasite decorrente de sobrecarga de carboidratos em um rebanho de 238 bezerros, com idades entre 12 e 15 meses, causada pela ingestão dos frutos de Enterolobium contortisiliquum. As taxas de morbidade, mortalidade e letalidade foram de, respectivamente, 12,7%, 5,2% e 42,1%. Clinicamente, os bovinos apresentaram fotossensibilização, salivação e diarreia. Os achados de necropsia foram semelhantes nos dois bezerros necropsiados e consistiram de fotodermatite e rumenite ulcerativa multifocal, subaguda a crônica, e abomasite. A relevância deste relato é que, pela primeira vez, foi possível associar a ocorrência da rumenite devido à sobrecarga de carboidratos com a intoxicação espontânea por E. contortisiliquum em bovinos, confirmando achados anteriormente descritos em experimentos realizados com ovinos.(AU)
Assuntos
Animais , Bovinos , Intoxicação por Plantas/veterinária , Rúmen/patologia , Acidose/veterinária , Abomaso/patologia , Transtornos de Fotossensibilidade/veterinária , Plantas Tóxicas , Fabaceae/toxicidadeRESUMO
We investigated the in vitro acaricide activity of the methanolic extract (ME) and alkaloid-rich fraction (AF) of Prosopis juliflora on Rhipicephalus microplus and correlated this effect with acetylcholinesterase (AChE) inhibition. The acaricide activity was evaluated using adult and larval immersion tests. Also, we studied the possible interaction mechanism of the major alkaloids present in this fraction via molecular docking at the active site of R. microplus AChE1 (RmAChE1). Higher reproductive inhibitory activity of the AF was recorded, with effective concentration (EC50) four times lower than that of the ME (31.6 versus 121 mg/mL). The AF caused mortality of tick larvae, with lethal concentration 50% (LC50) of 13.8 mg/mL. Both ME and AF were seen to have anticholinesterase activity on AChE of R. microplus larvae, while AF was more active with half-maximal inhibitory concentration (IC50) of 0.041 mg/mL. The LC-MS/MS analyses on the AF led to identification of three alkaloids: prosopine (1), juliprosinine (2) and juliprosopine (3). The molecular docking studies revealed that these alkaloids had interactions at the active site of the RmAChE1, mainly relating to hydrogen bonds and cation-pi interactions. We concluded that the alkaloids of P. juliflora showed acaricide activity on R. microplus and acted through an anticholinesterase mechanism.(AU)
A atividade carrapaticida in vitro do extrato metanólico (EM) e da fração de alcaloides (FA) de Prosopis juliflora foi investigada, frente ao Rhipicephalus microplus, e relacionada com a inibição da enzima acetilcolinesterase (AChE). A predição in silico das interações de alcaloides dessa fração com a AChE1 de R. microplus (RmAChE1) foi realizada por acoplamento molecular. A atividade carrapaticida foi avaliada, utilizando-se os ensaios de imersão de adultos e larvas. Maior efeito sobre parâmetros reprodutivos de teleóginas foi verificado para a FA, com valor de Concentração Efetiva 50% (CE50) (31.6 mg/mL), quatro vezes menor do que o valor do EM (121 mg/mL). A FA induziu mortalidade de larvas (Concentração Letal de 50% - CL50 = 13,8 mg/mL). A inibição da atividade da AChE de larvas do carrapato foi observada para EM e FA, sendo a FA mais ativa (Concentração Inibitória 50%- CI50 de 0,041mg/mL). As análises químicas da FA permitiram a identificação dos alcaloides prosopina (1), juliprosinina (2) e juliprosopina (3). No ensaio in silico, observou-se que esses alcaloides podem interagir com o sítio ativo da RmAChE1, principalmente por ligações de hidrogênio e interações cátion-pi. Os alcaloides de P. juliflora têm atividade carrapaticida contra R. microplus, atuando através do mecanismo anticolinesterásico.(AU)
Assuntos
Fabaceae/parasitologia , Fabaceae/toxicidade , Acaricidas/análise , Acaricidas/química , AlcaloidesRESUMO
The objective of this study was to determine the cytotoxicity of organic extracts of P. moniliformis in vitro and identify the acute toxicity and genotoxicity in vivo. The leaves were extracted using three organic solvents (cyclohexane [EP1], ethyl acetate [EP2], and methanol [EP3]). Phytochemical qualitative analysis was performed by thin layer chromatography (TLC). Cytotoxicity tests were performed on human embryonic kidney (HEK) cells and J774 murine macrophages. Acute toxicity in mice was measured after intraperitoneal (ip) administration of 2000 mg/kg, while evaluation of genotoxicity and mutagenicity were assessed using the comet assay and the micronucleus (MN) test, respectively. The TLC analysis of the extracts revealed the presence of flavonoids, triterpenes, steroids, and saponins. In the cytotoxicity assay, extracts EP1 and EP3 altered proliferation of HEK cells, and all organic extracts increased the viability of J774 cells. In the toxicity tests, no deaths or behavioral alterations were observed in mice exposed to the acute dose of the extracts. Although some extracts led to changes in hematological and histological parameters, these results did not indicate physiological changes. In relation to the MN test and comet assay, no significant changes were detected in the DNA of the animals tested with the extracts EP1, EP2, and EP3. Thus, extracts of P. moniliformis were not considered to be toxic and did not induce formation of MN or damage to cellular DNA in the genotoxicity tests.
Assuntos
Citotoxinas/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Fabaceae/toxicidade , Mutagênese/efeitos dos fármacos , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/toxicidade , Animais , Células Cultivadas/efeitos dos fármacos , Fabaceae/química , Humanos , Rim/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Animais , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Plantas Medicinais/toxicidadeRESUMO
As intoxicações em animais de produção causadas por plantas são bastante relatadas, resultando em perdas econômicas diretas causadas pela morte dos animais, diminuição dos índices produtivos e reprodutivos, além de aumentar a ocorrência e susceptibilidade a outras doenças. Já as perdas indiretas, incluem os custos para o controle das plantas tóxicas nas pastagens, além das medidas de manejo como a utilização de cercas e o pastoreio alternativo para evitar as intoxicações, assim como também os gastos associados ao diagnóstico e tratamento. No presente trabalho relatou-se a intoxicação de um bovino de raça Girolando de 11 anos pelo consumo da planta conhecida como bordão-de-velho (Samanea tubulosa). As alterações pós-mortem macro e microscópicas demonstraram que a causa provável de morte foi a síndrome de disfunção de múltiplos órgãos. Estudos in vivo são necessários para conhecer mais a fundo o potencial tóxico desta planta.
Intoxications in production animals caused by plants are well reported, resulting direct losses caused by the death of animals, by the reduction of productive and reproductive indexes, as well as increase in the frequence and susceptibility to other diseases. Indirect losses can be attributed to control plants in pastures, in addition to manipulation measures, such as use of fences and alternative grazing to avoid intoxication. The present work reported the intoxication of an 11-year-old female breed of cattle by the consumption of the plant known as bordão-develho (Samanea tubulosa). Macro and microscopic finds demonstrate that the probable cause is multiple organ dysfunction syndrome. In vivo studies are needed to know more about the toxic potential of this plant.
Assuntos
Feminino , Animais , Gravidez , Bovinos , Evolução Fatal , Fabaceae/toxicidade , Intoxicação por Plantas/veterináriaRESUMO
As intoxicações em animais de produção causadas por plantas são bastante relatadas, resultando em perdas econômicas diretas causadas pela morte dos animais, diminuição dos índices produtivos e reprodutivos, além de aumentar a ocorrência e susceptibilidade a outras doenças. Já as perdas indiretas, incluem os custos para o controle das plantas tóxicas nas pastagens, além das medidas de manejo como a utilização de cercas e o pastoreio alternativo para evitar as intoxicações, assim como também os gastos associados ao diagnóstico e tratamento. No presente trabalho relatou-se a intoxicação de um bovino de raça Girolando de 11 anos pelo consumo da planta conhecida como bordão-de-velho (Samanea tubulosa). As alterações pós-mortem macro e microscópicas demonstraram que a causa provável de morte foi a síndrome de disfunção de múltiplos órgãos. Estudos in vivo são necessários para conhecer mais a fundo o potencial tóxico desta planta.(AU)
Intoxications in production animals caused by plants are well reported, resulting direct losses caused by the death of animals, by the reduction of productive and reproductive indexes, as well as increase in the frequence and susceptibility to other diseases. Indirect losses can be attributed to control plants in pastures, in addition to manipulation measures, such as use of fences and alternative grazing to avoid intoxication. The present work reported the intoxication of an 11-year-old female breed of cattle by the consumption of the plant known as bordão-develho (Samanea tubulosa). Macro and microscopic finds demonstrate that the probable cause is multiple organ dysfunction syndrome. In vivo studies are needed to know more about the toxic potential of this plant.(AU)
Assuntos
Animais , Feminino , Gravidez , Bovinos , Intoxicação por Plantas/veterinária , Evolução Fatal , Fabaceae/toxicidadeRESUMO
Background: Stryphnodendron fissuratum is a tree from the Brazilian Cerrado. Its fruit is toxic to cattle and can cause clinical digestive signs, hepatogenous photosensitization, and abortion. Cases of poisoning in cattle, goats and guinea pigs have been experimentally reproduced; however, photosensitization could not be reproduced. The aim of this work was to describe an outbreak of natural poisoning and experimental reproduction in cattle, both with hepatogenous photosensitization.Materials, Methods & Results: Its described and natural outbreak and an experimental poisoning. In the outbreak, three bovines in the acute phase and three in the chronic phase were examined. Blood samples were collected from all of these animals in order to measure serum levels of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), urea, and creatinine. The first three animals underwent necropsy and histopathological evaluation. The experiment was conducted with two nine-month-old calves that received an oral paste made with crushed S. fissuratum fruits mixed with water. These fruits were collected at a farm at which cattle poisoning cases had occurred. Blood samples were collected in order to measure serum levels of AST, GGT, urea, and creatinine, before plant administration and then daily during the experimental period. Skin biopsies were taken before plant administration and new one after the first signs of skin lesions. The natural outbreak affected 52 of 160 bovine (31 calves and 21 cows) in the lot. Two calves and 14 cows died. Clinical signs consisted of depression, ataxia, incoordination, behavioral changes, decubitus, and death. One animal that died and 36 others that recovered had photodermatitis. Necropsy findings in the animals consisted of bad corporal condition, pale kidneys, evidence of liver lobular pattern, dry rumen contents, and full bladder.[...](AU)