RESUMO
The main protease (Mpro) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and activity. In this study, we analyzed the Mpro interaction with EbSe, its analogues, and its metabolites with Cys, GSH, and albumin by molecular docking. We also simulated the electronic structure of the generated molecules by density functional theory (DFT) and explored the stability of EbSe and one of its best derivatives, EbSe-2,5-MeClPh, in the catalytic pocket of Mpro through covalent docking and molecular dynamics. Our results show that EbSe and its analogues bound to GSH/albumin have larger distance between the selenium atom of the ligands and the sulfur atom of Cys145 of Mpro than the other compounds. This suggests that EbSe and its GSH/albumin-analogues may have less affinity for the active site of Mpro. EbSe-2,5-MeClPh was found one of the best molecules, and in molecular dynamics simulations, it showed to undergo more conformational changes in the active site of Mpro, in relation to EbSe, which remained stable in the catalytic pocket. Moreover, this study also reveals that all compounds have the potential to interact closely with the active site of Mpro, providing us with a concept of which derivatives may be promising for in vitro analysis in the future. We propose that these compounds are potential covalent inhibitors of Mpro and that organoselenium compounds are molecules that should be studied for their antiviral properties.
Assuntos
COVID-19 , Compostos Organosselênicos , Selênio , Humanos , Domínio Catalítico , Simulação de Acoplamento Molecular , SARS-CoV-2 , Albuminas , Azóis/farmacologia , Cisteína , Glutationa , Simulação de Dinâmica Molecular , Compostos Organosselênicos/farmacologia , Peptídeo Hidrolases , Inibidores de Proteases , Antivirais/farmacologiaRESUMO
The antioxidant effects of selenium as a component of selenoproteins has been thought to modulate host immunity and viral pathogenesis. Accordingly, the association of low dietary selenium status with inflammatory and immunodeficiency has been reported in the literature; however, the causal role of selenium deficiency in chronic inflammatory diseases and viral infection is still undefined. The COVID-19, characterized by acute respiratory syndrome and caused by the novel coronavirus 2, SARS-CoV-2, has infected millions of individuals worldwide since late 2019. The severity and mortality from COVID-19 have been associated with several factor, including age, sex and selenium deficiency. However, available data on selenium status and COVID-19 are limited, and a possible causative role for selenium deficiency in COVID-19 severity has yet to be fully addressed. In this context, we review the relationship between selenium, selenoproteins, COVID-19, immune and inflammatory responses, viral infection, and aging. Regardless of the role of selenium in immune and inflammatory responses, we emphasize that selenium supplementation should be indicated after a selenium deficiency be detected, particularly, in view of the critical role played by selenoproteins in human health. In addition, the levels of selenium should be monitored after the start of supplementation and discontinued as soon as normal levels are reached. Periodic assessment of selenium levels after supplementation is a critical issue to avoid over production of toxic metabolites of selenide because under normal conditions, selenoproteins attain saturated expression levels that limits their potential deleterious metabolic effects.
Assuntos
COVID-19 , Selênio , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Systemic candidiasis is produced by Candida albicans or non-albicans Candida species, opportunistic fungi that produce both superficial and invasive infections. Despite the availability of a wide range of antifungal agents for the treatment of candidiasis, failure of therapy is observed frequently, which opens new avenues in the field of alternative therapeutic strategies. METHODS: The effects of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2], a synthetic organic selenium (organochalcogen) compound, were investigated on virulence factors of C. krusei and compared with its antifungal effects on the virulence factors related to adhesion to cervical epithelial cell surfaces with C. albicans. RESULTS: (MeOPhSe)2, a compound non-toxic in epithelial (HeLa) and fibroblastic (Vero) cells, inhibited the growth in a dose-dependent manner and changed the kinetics parameters of C. krusei and, most importantly, extending the duration of lag phase of growth, inhibiting biofilm formation, and changing the structure of biofilm. Also, (MeOPhSe)2 reduced C. albicans and C. krusei adherence to cervical epithelial cells, an important factor for the early stage of the Candida-host interaction. The reduction was 37.24 ± 2.7 % in C. krusei (p = 0.00153) and 32.84 ± 3.2 % in C. albicans (p = 0.0072) at 20 µM (MeOPhSe)2, and the effect is in a concentration-dependent manner. Surprisingly, the antifungal potential on adhesion was similar between both species, indicating the potential of (MeOPhSe)2 as a promising antifungal drug against different Candida infections. CONCLUSION: Overall, we demonstrated the potential of (MeOPhSe)2 as an effective antifungal drug against the virulence factors of Candida species.
Assuntos
Antifúngicos , Selênio , Antifúngicos/química , Antifúngicos/farmacologia , Derivados de Benzeno , Biofilmes , Candida , Candida albicans , Células Epiteliais , Testes de Sensibilidade Microbiana , Compostos Organosselênicos , Pichia , Selênio/metabolismo , Selênio/farmacologia , Fatores de Virulência/metabolismo , Fatores de Virulência/farmacologiaRESUMO
INTRODUCTION: The incorporation of selenium in the structure of nucleosides is a promising strategy to develop novel therapeutic molecules. OBJECTIVE: To assess the toxic effects of three AZT derivatives containing organoselenium moieties on human erythrocytes. METHODOLOGY: Freshly human erythrocytes were acutely treated with AZT and selenium derivatives SZ1 (chlorophenylseleno), SZ2 (phenylseleno) and SZ3 (methylphenylseleno) at concentrations ranging from 10 to 500⯵M. Afterwards, parameters related to membrane damage, redox dyshomeostasis and eryptosis were determined in the cells. RESULTS: The effects of AZT and derivatives toward erythrocytes differed considerably. Overall, the SZ3 exhibited similar effect profiles to the prototypal AZT, without causing cytotoxicity. Contrary, the derivative SZ1 induced hemolysis and increased the membrane fragility of cells. Reactive species generation, lipid peroxidation and thiol depletion were also substantially increased in cells after exposure to SZ1. δ-ALA-D and Na+/K+-ATPase activities were inhibited by derivatives SZ1 and SZ2. Additionally, both derivatives caused eryptosis, promoting cell shrinkage and translocation of phosphatidylserine at the membrane surface. The size and granularity of erythrocytes were not modified by any compound. CONCLUSION: The insertion of either chlorophenylseleno or, in a certain way, phenylseleno moietes in the structure of AZT molecule was harmful to erythrocytes and this effect seems to involve a pro-oxidant activity. This was not true for the derivative encompassing methylphenylseleno portion, making it a promising candidate for pharmacological studies.
Assuntos
Azidas/efeitos adversos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Selênio/metabolismo , Zidovudina/efeitos adversos , Azidas/química , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bioactive phytocompounds are studied by several bioactivities demonstrated, as their cytotoxic effects. The aim of this work was to evaluate the phytochemical profile, the toxic effect using the Drosophila melanogaster animal model and the anti-inflammatory and antimicrobial effect of the Alternanthera brasiliana (EEAB) ethanol extract. The phytochemical profile was performed using HPLC. The cytotoxic effect was evaluated in vivo using D. melanogaster. The anti-inflammatory effect was determined by neurogenic and antiedematogenic assays, and the antimicrobial activity was assayed using a microdilution method to determine the minimum inhibitory concentration (MIC) of the EEAB alone and in association with antibiotics. The main compound identified on the EEAB was luteolin (1.93%). Its cytotoxic effect was demonstrated after 24 h in the concentrations of 10, 20 and 40 mg/mL. The extract demonstrated an antiedematogenic effect, with a reduction of the edema between 35.57 and 64.17%. The MIC of the extract was ≥1.024 µg/mL, thus being considered clinically irrelevant. However, when the EEAB was associated with gentamicin, a synergism against all bacterial strains assayed was observed: Staphylococcus aureus (SA10), Escherichia coli (EC06) and Pseudomonas aeruginosa (PA24). Due to these results, the EEAB demonstrated a low toxicity in vivo and anti-inflammatory and synergistic activities. These are promising results, mainly against microbial pathogens, and the compounds identified can be a source of carbon backbones for the discovery and creation of new drugs.
Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Amaranthaceae/química , Animais , Anti-Infecciosos/química , Escherichia coli/química , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos , Pseudomonas aeruginosa/química , Staphylococcus aureus/químicaRESUMO
Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.
Assuntos
Antioxidantes/metabolismo , Quelantes/metabolismo , Mercúrio/metabolismo , Folhas de Planta/química , Psidium/química , Saccharomyces cerevisiae/efeitos dos fármacos , Compostos de Bifenilo/química , Peroxidação de Lipídeos/efeitos dos fármacos , Picratos/química , Extratos Vegetais/química , Saccharomyces cerevisiae/fisiologiaRESUMO
Lantana camara, the widely studied species, and L. montevidensis, the less studied species of the genus Lantana are both used in traditional medicine for the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is known about the toxicity of L. montevidensis and there is limited information on its chemical constituents. Here, we investigated for the first time the genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from the leaves of Lantana montevidensis in human leukocytes, as well as their possible interaction with human erythrocyte membranes in vitro. The antioxidant activities of both extracts were also investigated in chemical and biological models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 µg/mL) did not affect DNA damage index, but promoted cytotoxicity at higher concentrations (240-480 µg/mL). Both extracts did not modify the osmotic fragility of human erythrocytes. The extracts scavenged DPPH radical and prevented Fe2+-induced lipid peroxidation in rat's brain and liver homogenates, and this was likely not attributed to Fe (II) chelation. The HPLC analysis of the extracts showed different amounts of polyphenolic compounds (isoquercitrin, gallic acid, catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin, quercetin, chlorogenic acid, luteolin) that may have contributed to these effects. These results supported information on the functional use of L. montevidensis in folk medicine.
RESUMO
Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal disorders and hypertension. However, scanty information exist on its potential toxicity to human, and little is known on its antioxidant activity in biological system. Hence, we investigated for the first time the potential toxic effects of ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and erythrocytes, as well as its influence on membrane erythrocytes osmotic fragility. In addition, EEEU was chemically characterized and its antioxidant capacity was evaluated. We found that EEEU (1-480µg/mL) caused neither cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay, respectively. EEEU (1-480µg/mL) did not have any effect on membrane erythrocytes fragility. In addition, EEEU inhibited Fe2+-induced lipid peroxidation in rat brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some polyphenolic compounds with high content such as quercetin, quercitrin, isoquercitrin, luteolin and ellagic acid, which may be at least in part responsible for its beneficial effects. Our results suggest that consumption of EEEU at relatively higher concentrations may not result in toxicity. However, further in vitro and in vivo studies should be conducted to ascertain its safety.
Assuntos
Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solventes/química , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Compostos de Bifenilo/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ensaio Cometa , Relação Dose-Resposta a Droga , Eritrócitos/metabolismo , Etanol/química , Eugenia/química , Humanos , Leucócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fragilidade Osmótica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Picratos/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta , Plantas Medicinais , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Medição de Risco , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)2 (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)2 and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)2 and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)2 could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.
Assuntos
Derivados de Benzeno/farmacologia , Fígado/química , Fígado/efeitos dos fármacos , Mercúrio/análise , Compostos de Metilmercúrio/farmacologia , Compostos Organosselênicos/farmacologia , Selênio/análise , Animais , Derivados de Benzeno/administração & dosagem , Masculino , Espectrometria de Massas , Compostos de Metilmercúrio/administração & dosagem , Mitocôndrias Hepáticas/química , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Compostos Organosselênicos/administração & dosagem , Ratos , Ratos WistarRESUMO
The aim of the present study was to assess the effects of zinc edetate on the oxidative stress of lambs infected by Haemonchus contortus. Twenty-four lambs were allocated into four groups: Group I--uninfected animals; Group II--uninfected animals treated subcutaneously with zinc edetate; Group III--animals infected by H. contortus and Group IV--animals infected and treated. The oxidative stress index (OSI) and the eggs per gram of feces (EPG) were assessed after 10, 17, 24, 31 and 38 days post-infection. Based on the EPG and the quantity of adult H. contortus, the infection did not differ between groups III and IV. Zinc edetate reduced the OSI in Group IV in relation to Group I after 24 days post-infection, and in relation to group III after 31 days post-infection. Treatment with zinc edetate could help reduce the oxidative stress induced by H. contortus in lambs.
Assuntos
Ácido Edético/farmacologia , Hemoncose/veterinária , Estresse Oxidativo/efeitos dos fármacos , Doenças dos Ovinos/parasitologia , Animais , Ácido Edético/administração & dosagem , Ácido Edético/química , Fezes/parasitologia , Feminino , Haemonchus , Masculino , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/patologia , Zinco/farmacologiaRESUMO
BACKGROUND: Gastrointestinal nematodes cause significant economic losses in the sheep industry, with frequent reports of anthelmintic resistance. Therefore, alternative methods to control these parasites are necessary. Thus, the aim of the present study was to assess the effect of treatment with selenium and copper on the protein profile of sheep that were experimentally infected with Haemonchus contortus. METHODS: Twenty-eight lambs were experimentally infected with H. contortus and divided into four experimental groups as follow: G1--untreated animals; G2--treated with sodium selenite; G3--treated with copper; G4--treated with sodium selenite and copper. The serum protein, body weight and egg count per gram of feces (EPG) were assessed at the baseline and after 20, 40, 60 and 80 days. The parasite burden was assessed 80 days after the beginning of the experiment. RESULTS: Higher levels of total protein and gamma globulin were observed in the lambs treated with sodium selenite and copper on D80. Copper acted as a growth promoter. The copper-supplemented groups exhibited higher daily and total weight gain. The association of selenium and copper altered the protein profile of sheep. Copper and selenium supplementation reduced EPG and worm burden at the end of the experiment. To the best of our knowledge, this is the first study to demonstrate the positive effect of the combined parenteral supplementation of Se and Cu on H. contortus infection. CONCLUSIONS: This injectable supplementation could be used as an auxiliary method to control H. contortus in sheep.
Assuntos
Cobre/farmacologia , Hemoncose/veterinária , Haemonchus , Doenças dos Ovinos/parasitologia , Selenito de Sódio/farmacologia , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cobre/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais , Esquema de Medicação , Fezes/parasitologia , Hemoncose/metabolismo , Masculino , Contagem de Ovos de Parasitas , Ovinos , Doenças dos Ovinos/metabolismo , Selenito de Sódio/administração & dosagemRESUMO
The aim of this study was to evaluate the effects of selenium and copper on oxidative stress and its performance in lambs experimentally infected with Haemonchus contortus. Twenty-eight five-months old lambs were experimentally infected by the oral route with 5000 third-stage infective larvae and allocated into four groups, i.e., untreated animals, animals treated intramuscularly with sodium selenite (0.2 mg kg(-1)), animals treated subcutaneously with copper (3.5 mg kg(-1)), and animals treated with sodium selenite (IM; 0.2 mg kg(-1)) and copper (SC; 3.5 mg kg(-1)). These animals received oat hay (Avena sativa) and commercial concentrate, totaling 15% of crude protein, 30% being derived from oat hay and 70% of the concentrate. Lipid peroxidation, antioxidant enzymes, eggs per gram of feces (EPG) and body weight were assessed on the day of infection and after 20, 40, 60 and 80 days post-infection. The number of H. contortus adults was assessed at the end of the experiment. The selenium associated or not with copper reduced the effects of oxidative stress caused by infection. The groups supplemented with copper had increased body weight, and the combination of these two minerals reduced the EPG and number of H. contortus adults in lambs. The use of selenium associated with copper may help the control of infection by H. contortus.
Assuntos
Antioxidantes/administração & dosagem , Cobre/administração & dosagem , Hemoncose/veterinária , Ácido Selênico/administração & dosagem , Doenças dos Ovinos/prevenção & controle , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catalase/sangue , Cobre/farmacologia , Cobre/uso terapêutico , Fezes/parasitologia , Glutationa Peroxidase/sangue , Hemoncose/tratamento farmacológico , Hemoncose/imunologia , Hemoncose/prevenção & controle , Hematócrito/veterinária , Imunocompetência/efeitos dos fármacos , Injeções Intramusculares/veterinária , Injeções Subcutâneas/veterinária , Peroxidação de Lipídeos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Contagem de Ovos de Parasitas/veterinária , Ácido Selênico/farmacologia , Ácido Selênico/uso terapêutico , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/imunologia , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Aumento de PesoRESUMO
Diabetes mellitus (DM) is associated with brain alterations that may contribute to cognitive dysfunctions. Chlorogenic acid (CGA) and caffeine (CA), abundant in coffee (CF), are natural compounds that have showed important actions in the brain. The present study aimed to evaluate the effect of CGA, CA, and CF on acetylcholinesterase (AChE), Na(+), K(+)-ATPase, aminolevulinate dehydratase (δ-ALA-D) activities and TBARS levels from cerebral cortex, as well as memory and anxiety in streptozotocin-induced diabetic rats. Animals were divided into eight groups (n = 5-10): control; control/CGA 5 mg/kg; control/CA 15 mg/kg; control/CF 0.5 g/kg; diabetic; diabetic/CGA 5 mg/kg; diabetic/CA 15 mg/kg; and diabetic/CF 0.5 g/kg. Our results demonstrated an increase in AChE activity and TBARS levels in cerebral cortex, while δ-ALA-D and Na(+), K(+)-ATPase activities were decreased in the diabetic rats when compared to control water group. Furthermore, a memory deficit and an increase in anxiety in diabetic rats were observed. The treatment with CGA and CA prevented the increase in AChE activity in diabetic rats when compared to the diabetic water group. CGA, CA, and CF intake partially prevented cerebral δ-ALA-D and Na(+), K(+)-ATPase activity decrease due to diabetes. Moreover, CGA prevented diabetes-induced TBARS production, improved memory, and decreased anxiety. In conclusion, among the compounds studied CGA proved to be a compound which acts better in the prevention of brain disorders promoted by DM.
Assuntos
Comportamento Animal/efeitos dos fármacos , Cafeína/farmacologia , Ácido Clorogênico/farmacologia , Café , Diabetes Mellitus Experimental/tratamento farmacológico , Acetilcolinesterase/biossíntese , Animais , Ansiedade/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Córtex Cerebral/metabolismo , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Sintase do Porfobilinogênio/biossíntese , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/biossíntese , Estreptozocina , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Vitex megapotamica (Sprengel) Moldenke belongs to the Verbenaceae family and is popularly known as "tarumã". The antioxidant capacity of fractions and crude extract from the leaves of V. megapotamica were determined in this study through the capacity to remove reactive species and phenolic compounds were quantified in the various fractions. The IC50 (DPPH) ranged from 14.17 ± 0.76 to 37.63 ± 0.98 µg/mL. The ethyl acetate fraction might contain the strongest lipid peroxidation inhibitory compounds with an IC50 of 16.36 ± 5.09 µg/mL, being also the one with the highest content of polyphenols (522.4 ± 1.12 mg/g), flavonoids (220.48 ± 0.30 mg/g) and condensed tannins (3.86 ± 0.53 mg/g). Compounds quantified by HPLC/DAD in the crude extract and fractions were chlorogenic and rosmarinic acids. Higher dosages of the extracts were more effective in reducing levels of plasma protein carbonyls and were also shown to be able to remove reactive species by a 2',7'-dichlorofluorescein diacetate assay, reducing oxidative stress in all tested fractions. Results obtained indicated that V. megapotamica exhibits good potential to prevent diseases caused by the overproduction of free radicals and it might also be used as a potential source of natural antioxidant agents.
Assuntos
Antioxidantes/análise , Flavonoides/análise , Polifenóis/análise , Taninos/análise , Vitex/química , Antioxidantes/química , Antioxidantes/farmacologia , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão , Cinamatos/análise , Depsídeos/análise , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Polifenóis/química , Polifenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Ácido RosmarínicoRESUMO
Knowledge of medicinal plants is often the only therapeutic resource of many communities and ethnic groups. "Erva-baleeira", Cordia verbenacea DC., is one of the species of plants currently exploited for the purpose of producing a phytotherapeutic product extracted from its leaves. In Brazil, its major distribution is in the region of the Atlantic Forest and similar vegetation. The crude extract is utilized in popular cultures in the form of hydroalcoholic, decoctions and infusions, mainly as antimicrobial, anti-inflammatory and analgesic agents. The aim of the present study was to establish a chemical and comparative profile of the experimental antibacterial activity and resistance modifying activity with ethnopharmacological reports. Phytochemical prospecting and HPLC analysis of the extract and fractions were in agreement with the literature with regard to the presence of secondary metabolites (tannins and flavonoids). The extract and fraction tested did not show clinically relevant antibacterial activity, but a synergistic effect was observed when combined with antibiotic, potentiating the antibacterial effect of aminoglycosides. We conclude that tests of antibacterial activity and modulating the resistance presented in this work results confirm the ethnobotanical and ethnopharmacological information, serving as a parameter in the search for new alternatives for the treatment of diseases.
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SCOPE: To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). METHODS AND RESULTS: On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. CONCLUSION: Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.
Assuntos
Cafeína/farmacologia , Bebidas Energéticas , Neurônios/metabolismo , Neurônios/patologia , Paullinia/química , Espécies Reativas de Oxigênio/metabolismo , Taurina/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Contagem de Células , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo , Humanos , Radical Hidroxila/metabolismo , Espaço Intracelular/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Modelos Biológicos , Degeneração Neural/patologia , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuritos/patologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.
Assuntos
Antioxidantes/uso terapêutico , Carya/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Eritrócitos/diagnóstico por imagem , Eritrócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Masculino , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Nozes/química , Picratos/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/química , UltrassonografiaRESUMO
Jatropha isabellei Müll Arg. belongs to the family Euphorbiaceae. The antioxidant capacity of this plant was evaluated by the DPPH method and inhibition of thiobarbituric acid reactive substances (TBARS). Ethyl acetate fraction demonstrated the best antioxidant capacity against the DPPH free radical and its profile was similar to ascorbic acid. This fraction also presented the best results of phenolics, flavonoids and condensed tannins, showing a positive relation between the phenolic content and antioxidant activity. All fractions and the crude extract were able to inhibit significantly the TBARS production induced by Fe(II) for the two tested concentrations, reaching the basal levels. In this test, ethyl acetate and dichloromethane fraction showed good values for inhibitory concentration. The dichloromethane fraction showed the best results against the fungi Sporothrix schenckii and Fusarium proliferatum and the bacterium of Micrococcus genus. This fraction allowed the isolation of acetil aleuritolic acid and a mixture of sitosterol 3-O-ß-D-glucoside and stigmasterol, described for the first time in this species.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Jatropha/química , Animais , Anti-Infecciosos/química , Antioxidantes/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Flavonoides/análise , Sequestradores de Radicais Livres/farmacologia , Fusarium/efeitos dos fármacos , Glucosídeos/química , Glucosídeos/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estrutura Molecular , Fenóis/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos Wistar , Sitosteroides/química , Sitosteroides/isolamento & purificação , Sporothrix/efeitos dos fármacos , Estigmasterol/isolamento & purificação , Taninos/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triterpenos/isolamento & purificaçãoRESUMO
Stryphnodendron rotundifolium is a phytotherapic used in the northeast of Brazil for the treatment of inflammatory processes which normally are associated with oxidative stress. Consequently, we have tested the antioxidant properties of hydroalcoholic (HAB) and aqueous extracts (AB) from the bark and aqueous extract (AL) from the leaves of Stryphnodendron rotundifolium to determine a possible association between antioxidant activity and the popular use of this plant. Free radical scavenger properties were assessed by the quenching of 1',1'-diphenil-2-picrylhydrazyl (DPPH) and the calculated IC(50) were: HAB = 5.4 ± 0.7, AB = 12.0 ± 2.6, and AL = 46.3 ± 12.3 µg/mL. Total phenolic contents were: HAB = 102.7 ± 2.8, AB = 114.4 ± 14.6, and AL = 93.8 ± 9.1 µg/mg plant). HPLC/DAD analyses indicated that gallic acid, catechin, rutin and caffeic acid were the major components of the crude extracts of S. rotundifolium. Plant extracts inhibited Fe(II)-induced lipid peroxidation in brain homogenates. Iron chelation was also investigated and only HBA exhibited a weak activity. Taken together, the results suggest that S. rotundifolium could be considered an effective agent in the prevention of diseases associated with oxidative stress.
Assuntos
Antioxidantes/farmacologia , Fabaceae/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiologia , Brasil , Cromatografia Líquida de Alta Pressão , Desoxirribose/química , Flavonoides/química , Flavonoides/isolamento & purificação , Quelantes de Ferro/química , Quelantes de Ferro/isolamento & purificação , Quelantes de Ferro/farmacologia , Masculino , Malondialdeído/metabolismo , Medicina Tradicional , Estresse Oxidativo , Fenóis/química , Fenóis/isolamento & purificação , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The objective of this study was to evaluate oxidative stress in lambs experimentally infected with Haemonchus contortus and supplemented with selenium and vitamin E. Twenty male Corriedale lambs were divided into four experimental groups with five animals each: G1 consisted of animals infected and supplemented with 0.2 mg/kg of live weight (LW) sodium selenite by intramuscular injection (IM); G2 consisted of animals infected with larvae and supplemented with 0.2 mg/kg LW sodium selenite IM and 2000 IU per animal of Vitamin E IM; G3 consisted of animals infected with larvae and supplemented with 2000 IU per animal of Vitamin E IM; and G4 consisted of animals infected with larvae. The animals were infected orally with 500 H. contortus larvae (L3) every 48 hours for 20 days. For biochemical analyses and eggs per grams of feces (EPG) evaluation, blood and feces were both collected at zero (T0), 20 (T1), 40 (T2) and 60 (T3) days. The weight of the animals was also measured at these times. Lower TBARS values were observed in the supplemented animals compared to the control group. The groups supplemented with Selenium exhibited blood GSH-Px activity higher than that of non-supplemented animals. Supplementation with selenium provided greater antioxidant protection against oxidative stress generated from experimental infection of lambs with H. contortus.