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The COVID-19 pandemic has substantially impacted the world health systems, causing public health concerns, and the search for new compounds with antiviral activity is of extreme interest. Natural molecules with bioactive potential are a trend, with essential oils (Eos) being the focus of recent studies. Thus, this study evaluates in chemico the d-limonene inhibitory activities in the viral genome of SARS-CoV-2 and analyzes the cytotoxic potential and safety profile of d-limonene and lime and orange EOs with a high content of d-limonene. The EOs were extracted and characterized, and the in chemico computational analysis for the determination as a potential anti-SARS-CoV-2 was performed with d-limonene, the major compound in EOs. The cytotoxicity analysis of EOs and d-limonene was carried out with MRC-5 and HaCaT, and the preliminary safety profile was also evaluated by the HET-CAM assay. d-limonene was suggested as a promising compound for anti-SARS-CoV-2 research, since the molecule does not provide mutagenic and cytotoxic fragments, and does not have irritating potential when diluted, in addition to having favorable pharmacokinetic characteristics, through in chemico analysis. Collectively, the results reveal the antiviral potential of lime and orange EOs, as well as their major compound. In this sense, further studies should be conducted to understand the antiviral mechanisms.
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Medicinal plants have been employed as an alternative method to treat diabetes. One is Cissus sicyoides, a plant from the Amazon region (Northern Brazil), which is morphologically similar to Wedelia paludosa, a plant easily found in Southern Brazil. Thus, this study aimed to assess the potential toxicity of C. sicyoides and W. paludosa's leaves water extracts. Through phytochemical screening, phenolic compounds and alkaloids were observed in both species and coumarins only W. paludosa's aqueous extract. Phenolic compounds were quantified in both extracts and C. sicyoides presented 1.36 ± 0.04 mg/pyrogalic acid equivalent (PAE), whereas W. paludosa presented 3.27 ± 0.07 mg/PAE. Total antioxidant power was measured by the ferric reduction assay. Cissus sicyoides exhibited total antioxidant activity of 748.0 ± 104.5 µM and W. paludosa, 1971.5 ± 141.0 µM. Cissus sicyoides showed an inhibition rate for the alpha-glucosidases enzyme assay of 55.2 ± 1.7% and W. paludosa, 85.8 ± 9.7%. The formation of reactive oxygen species was evaluated by the DCFH-DA method, its formation being higher in W. paludosa's water extracts than in C. sicyoides. Cell viability was evaluated by the Sulforhodamine B and MTT assays. Wedelia paludosa's extracts' exposure presented a cell viability close to positive control starting from 2 mg/mL to 30 mg/mL, whereas C. sicyoides demonstrated statistical significant low viability at the highest concentration when compared with the negative control. Moreover, cell death mechanism was investigated, having W. paludosa's extract indicated death by necrosis. The results suggest low toxicity for C. sicyoides' extract and high toxicity for W. paludosa's extract.
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Ulcerative colitis (UC) affects the mucosa and submucosa of the large intestine. One of the mechanisms involved in its etiology is oxidative stress (OS), directly involved in the inflammatory process characteristic of UC. The Campsiandra laurifolia, known as acapurana, was described as possessing antioxidant properties. We used 24 male Wistar rats, divided into control (CO), control + acapurana (CO + A), colitis (CL), and colitis + acapurana (CL + A) groups. This study performed histological analysis, measuring anal sphincter pressure (ASP) and lipoperoxidation (LPO). The activity of the antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated. The expression of the nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry. The statistical analysis used was the one-way analysis of variance (ANOVA), followed by the Student-Newman-Keuls test; values were expressed as mean ± standard error, and the significance level was p < 0.05. In the animals of the CL group, we observed the destruction of the crypts and the presence of mucosal ulcers, edema, and submucosal inflammatory infiltrate, as well as increased damage to the intestinal mucosa, reduced ASP, increased LPO and SOD activity, reduced GSH levels, and increased expression of NFkB and iNOS. The administration of C. laurifolia in the CL + A group was shown to cause regeneration of crypts, reduction of inflammatory infiltrate, reduction of damage to the intestinal mucosa, increase in ASP, and reduction in LPO with the restoration of SOD activity and GSH levels. The immunohistochemistry of NFkB and iNOS was significantly reduced. Therefore, the C. laurifolia aqueous extract appears to exert an antioxidant and anti-inflammatory effect in rats with AA-induced colitis. (AU)
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Animales , Ratas , Colitis Ulcerosa/etiología , Fabaceae , Antioxidantes , FN-kappa B , Óxido Nítrico Sintasa de Tipo II , Mucosa Intestinal/anatomía & histología , Peróxidos LipídicosRESUMEN
Brunfelsia uniflora (Pohl) D. Don roots have been widely used in folk medicine for treating inflammatory conditions. However, few studies have elucidated compounds that justify their traditional use. This study was conducted to characterize the phytochemical profile and evaluate the in vitro antioxidant capacity, and in vivo anti-inflammatory activity of extracts obtained from B. uniflora roots by comparing an herbal remedy (HR) with the crude hydroalcoholic extract (CHE). In the phytochemical analysis, scopoletin was identified as the marker compound. In quantitative analyses, CHE showed better results than HR. Furthermore, CHE had an effective anti-inflammatory activity. Animals treated with CHE (200 mg/kg) showed an 89.1% and a 73.8% reduction in edema volume after 1 hour of edema induction compared with those treated with negative control and positive control (indomethacin), respectively. These results show that B. uniflora root extracts have promising antioxidant and anti-inflammatory activities, thus corroborating their application in ethnomedicine.
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Antiinflamatorios , Extractos Vegetales , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Edema/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.
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Asteraceae/citología , Asteraceae/química , Asteraceae/toxicidad , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Vitaceae/citología , Vitaceae/química , Vitaceae/toxicidadRESUMEN
BACKGROUND: Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established based on patient's body surface area, an approach associated with large inter-individual variability in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1. Genetic polymorphisms in the UGT1A1 gene are associated to higher exposures to SN-38 and severe toxicity. Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available, with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization. The aim of this manuscript is to review the available evidence supporting pharmacogenetic and pharmacokinetic dose individualization of IRI in order to reduce the occurrence of severe toxicity during cancer treatment. METHODS: The PubMed database was searched, considering papers published in the period from 1995-2017, using the keywords irinotecan, pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, pharmacokinetics and pharmacodynamics, either alone or in combination, with original papers being selected based on the presence of relevant data. CONCLUSION: The findings of this review confirm the importance of considering individual patient characteristics to select IRI doses. Currently, the most straightforward approach for IRI dose individualization is UGT1A1 genotyping. However, this strategy is sub-optimal due to several other genetic and environmental contributions to the variable pharmacokinetics of IRI and its active metabolite. The use of dried blood spot sampling could allow the clinical application of limited sampling and population pharmacokinetic models for IRI doses individualization.
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Antineoplásicos/farmacocinética , Glucuronosiltransferasa/genética , Irinotecán/farmacocinética , Farmacogenética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Genotipo , Glucuronosiltransferasa/metabolismo , Humanos , Irinotecán/uso terapéutico , Irinotecán/toxicidad , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismoRESUMEN
Flavonoids are compounds responsible for several organoleptic characteristics of plant-derived foods. They are also bioactive compounds with antiinflammatory role. Different mechanisms for this activity have been reported, but their effects on cell migration are not fully understood. In the present study, the role of flavonoids on leukocyte migration in vivo was investigated, using the carrageenan-induced pleurisy model and intravital microscopy in rats. It was found that quercetin (1), rutin (2), flavone (5), apigenin (6) and flavonol (7) reduced cell migration to the pleural cavity and inhibited rolling, adhesion and transmigration. Additionally, flow cytometry assays showed that the in vitro treatment with all compounds (15-60 µM) did not cause cell death and 1 inhibited the cleavage of L-selectin and the ß2-integrin expression, whereas 2 and 7 only inhibited the ß2-integrin expression. Together, data herein presented clearly show the ability of flavonoids to inhibit in vivo neutrophil influx into inflamed tissue, by acting in different mechanisms of neutrophil migration.
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Antígenos CD18/metabolismo , Flavonoides/farmacología , Inflamación/metabolismo , Selectina L/metabolismo , Neutrófilos/efectos de los fármacos , Animales , Movimiento Celular/efectos de los fármacos , Endotelio/citología , Inflamación/inducido químicamente , Rodamiento de Leucocito , Masculino , Neutrófilos/metabolismo , Ratas , Ratas WistarRESUMEN
CONTEXT: Alternanthera brasiliana (L.) Kuntze (Amarantaceae) is widely used in Brazilian traditional medicine as an analgesic, anti-inflammatory and antibacterial. OBJECTIVE: To investigate the potential anti-inflammatory, analgesic, anxiolytic, and locomotor effect of the infusions in preclinical models. MATERIALS AND METHODS: Anti-inflammatory activity was evaluated by a carrageenan-induced pleurisy test in Wistar rats (200 and 400 mg/kg, n = 6-7). Analgesic activity was evaluated by the number of abdominal contractions induced by 0.6% acetic acid administered to Swiss mice (25, 50, 100, 200, and 400 mg/kg, n = 10). Effects on the central nervous system (CNS) were evaluated in Wistar rats (100, 200, and 400 mg/kg, n = 10) using open field and plus maze models. RESULTS AND DISCUSSION: Possible anti-inflammatory activity was indicated by the significant reduction of 19.8% for 200 mg/kg (p < 0.05) and 23.9% for 400 mg/kg (p < 0.05) of polymorphonuclear cells in pleural exudate. Analgesic activity was suggested by the significant reduction (p < 0.01) of number of abdominal contractions for all doses under study. No anxiolytic effect was noted, but there was an increase in the number of rearings in the group of rats treated with 100 mg/kg dose (p < 0.05). CONCLUSIONS: Our findings suggest that the aqueous extract of the leaves of A. brasiliana has a potential pharmacological effect on inflammation and pain.
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Amaranthaceae/química , Analgésicos/farmacología , Antiinflamatorios/farmacología , Extractos Vegetales/farmacología , Analgésicos/administración & dosificación , Analgésicos/aislamiento & purificación , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/aislamiento & purificación , Ansiolíticos/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Brasil , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Medicina Tradicional , Ratones , Actividad Motora/efectos de los fármacos , Neutrófilos/metabolismo , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Extractos Vegetales/administración & dosificación , Ratas , Ratas WistarRESUMEN
CONTEXT: Copaiba oil is an oleoresin made up of resin acids and volatile compounds, and it is obtained by tapping the trunks of trees that are members of the Copaifera L. (Leguminoseae) genus and are found in tropical parts of Latin America. OBJECTIVE: This study analyzed the chemical composition of Copaifera multijuga Hayne oil and conducted preclinical trials to investigate anti-inflammatory effects and any action it may have on the central nervous system (CNS) of rats. MATERIALS AND METHODS: The chemical analysis was carried out using gas chromatography with mass spectroscopy. Anti-inflammatory activity was measured by leucocytes mobilization, by chemotaxis assay in Boyden's chamber, and by pleurisy model in rats. CNS effect was determined by plus maze and open-field assays. The statistical test applied was analysis of variance (ANOVA) followed by Tukey's test or ANOVA followed by Duncan's test. RESULTS: The oil was composed of sesquiterpenes with the predominance of ß-caryophyllene (36.0%), followed by α-copaene (18.8%), ß-bisabolene (8.5%), and α-trans-bergamotene (7.0%). Data demonstrated that at 100 and 200 mg/kg doses and at a concentration of 200 µl/ml copaiba essential oil presented anti-inflammatory effects both in vivo and in vitro based on reduced leukocyte migration to the rats' pleural cavity and to the chemotactic agent lipopolysaccharide solution, respectively. During the experiments investigating CNS effects, locomotive and exploratory activities were reduced and the animals' anxiety increased at 100 and 200 mg/kg. CONCLUSION: The results obtained suggest that copaiba oil has an interesting anti-inflammatory effect and important effect on the CNS.
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Fabaceae , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Evaluación Preclínica de Medicamentos/métodos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratas , Ratas WistarRESUMEN
Flavonoids are polyphenols that are ubiquitous in plants and frequently consumed in the diet. They are suggested to have many beneficial actions on human health, including anti-inflammatory activity. Their properties have been studied in a number of cell types, but little is known about their effects on neutrophil biology. Consequently, we selected 25 flavonoids with different structural features to evaluate their in vitro inhibition of rat polymorphonuclear neutrophil (PMN) chemotaxis, employing a modified Boyden chamber. Migratory activity was measured towards a chemotactic stimulant, formyl-Met-Leu-Phe or lipopolysaccharide. Furthermore, the cytotoxic effect of flavonoids on PMNs was determined by the release of cytosolic lactate dehydrogenase (LDH). Ten flavonoids significantly retarded the migration of PMNs with at least one of the concentrations tested in a range between 0.625 and 100 µM; the best antichemotactic agents were flavone, flavonol, quercetin and rutin. None of the flavanones evaluated presented any significant inhibition of migration in this assay. Our findings indicated that non-hydroxylated flavones possess a better antichemotactic activity when compared to flavones with hydroxy groups. The presence of a sugar moiety in rutin did not produce any increase in this effect, when compared to the respective aglycone analogue. Finally, none of the flavonoids exhibited cell toxicity and for many of these flavonoids this is the first report of the inhibition of PMN chemotaxis.
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Quimiotaxis de Leucocito/efectos de los fármacos , Flavonoides/farmacología , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Achyrocline/química , Animales , Antiinflamatorios/farmacología , Inhibición de Migración Celular/efectos de los fármacos , Factores Quimiotácticos/antagonistas & inhibidores , Factores Quimiotácticos/farmacología , Citotoxinas/farmacología , Flavonoides/química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , N-Formilmetionina Leucil-Fenilalanina/antagonistas & inhibidores , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/inmunología , Extractos Vegetales/química , RatasRESUMEN
The objective of this research was to identify the effects of 3-week treatment of normal and streptozotocin-induced diabetic rats using a leaf decoction of Campomanesia xanthocarpa Berg. (20 g/L) on physiological, biochemical and histological parameters. Streptozotocin (STZ, 70 mg/kg in citrate buffer, pH 4.5) was administered IP to induce experimental diabetes one week prior to the treatment. STZ caused typical diabetic symptoms: polydypsia, polyuria, polyphagia, hyperglycemia, hypertriglyceridemia and histopathological modifications in the pancreas, liver and kidney. The treatment of diabetic rats using the decoction decreased blood glucose levels, inhibited hepatic glycogen loss, and prevented potential histopathological alterations in the pancreas and kidneys. No differences were found between the control rats treated with the decoction and the control rats maintained on water only. In conclusion, these results suggest that C. xanthocarpa leaf decoction (20g/L) might be useful for diabetes mellitus management, but further pharmacological and toxicological studies are needed.
O objetivo deste trabalho foi identificar os efeitos do tratamento com o decocto das folhas de Campomanesia xanthocarpa Berg. (20 g/L), durante 3 semanas, sobre parâmetros fisiológicos, bioquímicos e histológicos de ratos normais e diabéticos induzidos por estreptozotocina. O diabete melito foi induzido uma semana antes de iniciar o tratamento experimental, pela administração IP de estreptozotocina (STZ, 70 mg/kg em tampão citrato, pH 4.5). Os ratos tratados com STZ apresentaram sintomas típicos de diabete: polifagia, polidipsia, hiperglicemia, hipertrigliceridemia e alterações histopatológicas no pâncreas, fígado e rim. O tratamento dos ratos diabéticos com o decocto diminuiu os níveis de glicose sanguínea, inibiu a degradação do glicogênio hepático e preveniu possíveis alterações histopatológicas no pâncreas e no rim. Nos ratos controles tratados com o decocto não foram verificadas diferenças significativas em relação aos controles tratados com água. Em conclusão, os resultados sugerem que o tratamento com o decocto das folhas de C. xanthocarpa leaf decoction (20 g/L) possa ser útil para o manejo do diabete melito, porém estudos farmacológicos e toxicológicos ainda são necessários.
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Animales , Ratas , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/terapia , Extractos Vegetales , Diabetes Mellitus Experimental , Estructuras de las PlantasRESUMEN
O objetivo deste trabalho foi verificar o teor de quercetina obtido dos extratos de partes aéreas de Baccharis articulata (Lam.) Pers., Asteraceae, submetidas a diferentes técnicas de secagem, bem como a avaliação de sua atividade antioxidante in vitro. Foi verificada maior concentração deste flavonoide nas amostras secas em estufa, porém não houve diferença significativa na atividade farmacológica das amostras analisadas.
The objective of this work was to verify the influence of different drying processes on the levels of quercetin of the aerial parts of Baccharis articulata (Lam.) Pers., Asteraceae, as well as the evaluation of the in vitro antioxidant activity of these extracts. We demonstrated that the highest concentration of this flavonoid was detected in oven-dried samples, although there no significant difference in their pharmacological activity of all analyzed samples could be shown.
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OBJECTIVES: Free radicals may damage lipids, proteins and DNA, which may lead to critical diseases in the aging. This work evaluated levels of malondialdehyde (MDA), glutathione peroxidase (GPx) and DNA damage by comet assay (SCGE) in older adults that do exercises regularly. DESIGN AND METHODS: 110 females, aged 66.3+/-8 years were divided into sedentary (n=54), walking (n=36) and muscle building (n=20) groups. Levels of MDA, GPx and SCGE were measured in venous blood before and after exercise. RESULTS: MDA levels were higher (P<0.005) and GPx levels were lower (P<0.005) in active groups than in sedentary group. SCGE index after physical activity was greater than at baseline (muscle building: P=0.004; walking: P=0.002). CONCLUSIONS: Exercise reduces the diseases risk, but may promote the production of free radicals. It remains unclear whether cell adaptations responsible for health benefits are associated with such events. However we may suggest the existence of a different biochemical pattern for older adults that do exercise regularly.
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Daño del ADN , Ejercicio Físico , Estrés Oxidativo , Anciano , Ensayo Cometa , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Malondialdehído/metabolismo , Persona de Mediana EdadRESUMEN
Cardiovascular diseases affect millions of people and have high mortality and morbidity rates worldwide. Studies about the consumption of garlic and onion showed that these species have considerable beneficial effects against diseases such as hypertension, atherosclerosis and thrombosis, and are classifed, therefore, as functional foods. Their properties have been attributed to organosulfur compounds, particularly allicin, which are abundantly found in their tissues. This study reviewed the literature about the effects of garlic and onion on the cardiovascular system.
Enfermedades del sistema cardiovascular afectan millones de personas y son causadoras de elevados índices de mortalidad y morbilidad en el mundo. Estudios sobre el consumo de ajo y cebolla mostraron considerables beneficios en relación a enfermedades como hipertensión, trombosis y arterioesclerosis siendo considerados alimentos funcionales. Esas ventajas han sido atribuidas a la presencia en abundancia de compuestos orgánicos sulfurados en el tejido de esas plantas, destacándose entre ellos la aliicina. En este trabajo relatamos un estudio bibliográfico sobre la acción del ajo y la cebolla en el sistema cardiovascular.
As doenças do sistema cardiovascular atingem milhões de pessoas e são causadoras de elevado índice de mortalidade e morbidade mundial. Estudos realizados sobre o consumo do alho e cebola relataram que estas espécies apresentaram considerável efeito benéfico sobre enfermidades como hipertensão, aterosclerose e trombose, sendo desta forma, considerados como alimentos funcionais. Essas atividades têm sido atribuídas aos compostos orgânicos sulfurados, abundantes nos tecidos dessas plantas, destacando-se a aliicina. Desta forma, o presente estudo visa realizar um levantamento bibliográfico sobre o alho e a cebola quanto à sua ação sobre o sistema cardiovascular.