RESUMO
Smilax brasiliensis (Smilacaceae) is a native Brazilian plant found in the Cerrado biome and commonly used in folk medicine. The aim of this study was to evaluate the allelopathic, cytotoxic, genotoxic, and antigenotoxic potential of extract and fractions of Smilax brasiliensis leaves. Quercetin and rutin isomers were observed in the subfractions. The dichloromethane fraction (1000 µg/mL) decreased lettuce (Lactuca sativa) seed vigor, while and ethyl acetate and hydromethanol fractions (1000 µg/mL) affected the germination, and quercetin and rutin affected the vigor and germination of onion seeds. The extract, fractions, quercetin, and rutin inhibited or promoted lettuce hypocotyl and radicle growth. The extract and fractions inhibited onion hypocotyl growth at all concentrations. With regards to radicle growth, the results were diversified: growth was either inhibited or promoted. Rutin and quercetin inhibited onion hypocotyl and radicle growth at all concentrations. The extract and fractions of Smilax brasiliensis, rutin, and quercetin did not cause cytotoxic effect evaluated by mitotic index. The extract and fractions showed genotoxic effects. Quercetin and rutin did not cause genotoxic effects. On the other hand, the extract and fractions showed antigenotoxic effects at all tested concentrations, where they were able to revert chromosomal abnormalities caused by glyphosate. However, additional studies are required to evaluate the possible use of the S. brasiliensis leaf methanol extract and fractions as natural sources of bioherbicides.
Assuntos
Quercetina/toxicidade , Rutina/toxicidade , Smilax/química , Alelopatia , Citotoxinas/toxicidade , Dano ao DNA/efeitos dos fármacos , Germinação/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Folhas de Planta/química , Quercetina/farmacologia , Rutina/farmacologia , Sementes/efeitos dos fármacosRESUMO
Chagas disease is caused by the Trypanosoma cruzi affecting millions of people, and widespread throughout Latin America. This disease exhibits a problematic chemotherapy. Benznidazole, which is the drug currently used as standard treatment, lamentably evokes several adverse reactions. Among other options, natural products have been tested to discover a novel therapeutic drug for this disease. A lot of plants from the Brazilian flora did not contain studies about their biological effects. Restinga de Jurubatiba from Brazil is a sandbank ecosystem poorly studied in relation to plant biological activity. Thus, three plant species from Restinga de Jurubatiba were tested against in vitro antiprotozoal activity. Among six extracts obtained from leaves and stem parts and 2 essential oils derived from leave parts, only 3 extracts inhibited epimastigote proliferation. Substances present in the extracts with activity were isolated (quercetin, myricetin, and ursolic acid), and evaluated in relation to antiprotozoal activity against epimastigote Y and Dm28 Trypanosoma cruzi strains. All isolated substances were effective to reduce protozoal proliferation. Essentially, quercetin and myricetin did not cause mammalian cell toxicity. In summary, myricetin and quercetin molecule can be used as a scaffold to develop new effective drugs against Chagas's disease.
Assuntos
Antiprotozoários/isolamento & purificação , Ecossistema , Extratos Vegetais/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/toxicidade , Brasil , Linhagem Celular , Doença de Chagas/prevenção & controle , Flavonoides/toxicidade , Humanos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Quercetina/toxicidadeRESUMO
PURPOSE: This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and antioxidant effects as well as its toxicity. METHODS: The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated. RESULTS: The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-κB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU-NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE. CONCLUSIONS: These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Portadores de Fármacos/química , Emulsões/química , Lipídeos/química , Quercetina/administração & dosagem , Quercetina/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/toxicidade , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Células CACO-2 , Edema/tratamento farmacológico , Edema/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , NF-kappa B/análise , NF-kappa B/antagonistas & inibidores , Quercetina/farmacocinética , Quercetina/toxicidade , Ratos , Ratos WistarRESUMO
BACKGROUND: To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. METHODS: Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. RESULTS: At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. CONCLUSIONS: The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.
Assuntos
Antimaláricos/administração & dosagem , Antimaláricos/farmacologia , Caesalpinia/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Artemisininas/farmacologia , Artesunato , Brasil , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Malária/tratamento farmacológico , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Plasmodium chabaudi/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quercetina/administração & dosagem , Quercetina/isolamento & purificação , Quercetina/farmacologia , Quercetina/toxicidade , Doenças dos Roedores/tratamento farmacológico , Doenças dos Roedores/parasitologiaRESUMO
The flavonoid quercetin and its derivative rutin were investigated for genotoxicity/antigenotoxicity activity in human hepatoma HepG2 cells using the comet assay. The extract cytotoxicity was evaluated using the trypan blue exclusion dye method with quercetin and rutin concentrations ranging from 0.1 to 200.0 µg/mL of culture medium. Three minor non-cytotoxic concentrations were chosen to evaluate the genotoxicity and antigenotoxicity of the flavonoids (0.1, 1.0 and 5.0 µg/mL) through comet assay. The cultures were treated with three different concentrations of rutin or quercetin (genotoxicity) or their association with Aflatoxin B1 (AFB1), methyl methanesulfonate (MMS) or doxorubicin (DXR) (antigenotoxicity test) in three protocols: pre-treatment, simultaneous treatment and post-treatment. The cell cultures were also treated with 1% DMSO (control group), AFB1, MMS and DXR (positive-control). Statistical analyses were performed using ANOVA and Dunnett's test (p ≤ 0.05). Quercetin at concentrations higher than 10.0 µg/mL or rutin higher than 50.0 µg/mL exhibited a cytotoxic effect on the cells, showing that quercetin is more cytotoxic than rutin. Furthermore, neither compound was able to induce genotoxicity in the concentrations evaluated. On the other hand, both flavonoids reduced DNA damage induced by AFB1, MMS and DXR in all treatment protocols.
Assuntos
Dano ao DNA/efeitos dos fármacos , Quercetina/farmacologia , Rutina/farmacologia , Aflatoxina B1/toxicidade , Ensaio Cometa , Doxorrubicina/toxicidade , Fabaceae/química , Células Hep G2 , Humanos , Metanossulfonato de Metila/toxicidade , Quercetina/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Rutina/toxicidadeRESUMO
PURPOSE: In the present study, histological aspects were considered in order to evaluate the in vivo photoprotective effect of a w/o microemulsion containing quercetin against UVB irradiation-induced dermal damages. The toxicity in cell culture and the potential skin irritation resulting from topical application of this formulation were also investigated. METHODS: Mouse dorsal surfaces were treated topically with 300 mg of the unloaded and quercetin-loaded (0.3%, w/w) microemulsions before and after exposure to UVB (2.87 J/cm2) irradiation. The untreated control groups irradiated and non-irradiated were also evaluated. UVB-induced histopathological changes as well as the photoprotective effect of this formulation were evaluated considering the parameters of infiltration of inflammatory cells, epidermis thickening (basale and spinosum layers) and collagen and elastic fiber contents. The cytotoxicity of the reported formulation was evaluated in L929 mice fibroblasts by MTT assay and the skin irritation was investigated after topical application of both unloaded and quercetin-loaded microemulsions once a day for 15 days. RESULTS: The results demonstrated that the w/o microemulsion containing quercetin reduced the incidence of histological skin alterations, mainly the connective-tissue damage, induced by exposure to UVB irradiation, this allows the suggestion that protective effects of this formulation against UV-induced responses are not secondary to the interference of UV transmission (i.e., blocking the UVB radiation from being absorbed by the skin), as is usually done with UVB absorbers and sunscreens, but is instead due to different biological effects of this flavonoid. Furthermore, by evaluating the cytotoxic effect on L929 cells and histological aspects such as infiltration of inflammatory cells and epidermis thickness of hairless mice, the present study also demonstrated no toxicity of the proposed system. CONCLUSIONS: Therefore, based on these mouse models, a detailed characterization of the w/o microemulsion incorporating quercetin effects as a photochemoprotective agent on human skin is thus indicated.
Assuntos
Antioxidantes/farmacologia , Quercetina/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/administração & dosagem , Antioxidantes/toxicidade , Células Cultivadas , Colágeno/metabolismo , Elastina/metabolismo , Emulsões , Feminino , Fibroblastos/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Pelados , Quercetina/administração & dosagem , Quercetina/toxicidade , Pele/efeitos dos fármacos , Pele/efeitos da radiaçãoRESUMO
Davilla nitida and Davilla elliptica (Dilleniaceae) are plants that occur predominantly in the cerrado region of South America. They are used in popular medicine to treat stomach diseases, diarrhea and swelling, particularly of the lymph nodes and testicles. Chemical investigation of these two plant species led to the identification of the compounds myricetin-3-O-α-l-rhamnoside (myricitrin), quercetin-3-O-α-l-rhamnoside (quercitrin), myricetin, quercetin and gallic acid derivatives in the leaves of D. nitida and D. elliptica. Therefore, it was concluded that the two species of Davilla possess qualitatively similar chemical profiles. In the present study, the mutagenic and genotoxic potential of these plants and of their isolated compounds was tested in the Salmonella typhimurium assay (Ames test) with strains TA100, TA98, TA102 and TA97a, in the micronucleus test with peripheral blood cells of mice treated in vivo, and in plasmid DNA to analyze DNA strand-breaks. In the assessment of mutagenic potential by the Ames test, extracts from both plant species and a D. nitida ethyl-acetate fraction induced positive responses. On the other hand, none of the extracts showed genotoxic activity in the mouse cells. In the presence of metal ion, D. nitida and D. elliptica aqueous and ethyl-acetate fractions, as well as their isolated compounds, induced single- and double-strand-breaks in plasmid DNA in a cell-free system.
Assuntos
Dano ao DNA , Dilleniaceae , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Flavonoides/toxicidade , Ácido Gálico/toxicidade , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade/métodos , Folhas de Planta/química , Plasmídeos , Quercetina/análogos & derivados , Quercetina/toxicidade , Salmonella typhimurium/genéticaRESUMO
Methylmercury (MeHg) is a highly neurotoxic pollutant, whose mechanisms of toxicity are related to its pro-oxidative properties. A previous report showed under in vivo conditions the neuroprotective effects of plants of the genus Polygala against MeHg-induced neurotoxicity. Moreover, the flavonoid quercetin, isolated from Polygala sabulosa, displayed beneficial effects against MeHg-induced oxidative damage under in vitro conditions. In this study, we sought for potential beneficial effects of quercetin against the neurotoxicity induced by MeHg in Swiss female mice. Animals were divided into six experimental groups: control, quercetin low dose (5 mg/kg), quercetin high dose (50 mg/kg), MeHg (40 mg/L, in tap water), MeHg+quercetin low dose, and MeHg+quercetin high dose. After the treatment (21 days), a significant motor deficit was observed in MeHg+quercetin groups. Biochemical parameters related to oxidative stress showed that the simultaneous treatment with quercetin and MeHg caused a higher cerebellar oxidative damage when compared to the individual exposures. MeHg plus quercetin elicited a higher cerebellar lipid peroxidation than MeHg or quercetin alone. The present results indicate that under in vivo conditions quercetin and MeHg cause additive pro-oxidative effects toward the mice cerebellum and that such phenomenon is associated with the observed motor deficit.
Assuntos
Compostos de Metilmercúrio/toxicidade , Sistema Nervoso/efeitos dos fármacos , Quercetina/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Camundongos , Estresse OxidativoRESUMO
Byrsonima crassa is a plant pertaining to the Brazilian central savannah-like belt of vegetation and popularly used for the treatment of gastric dysfunctions and diarrhoea. The methanol extract contains catechin, tannins, terpenes and flavonoids; both mutagenic potential and antioxidant properties have been ascribed to flavonoids. The mutagenicity of some flavonoids is believed to be associated with the formation of reactive oxygen species and seems to depend on the number and position of hydroxyl groups. In the present study the mutagenic activity of the methanol, chloroform and 80% aqueous methanol extracts, as well as acetate and aqueous sub-fractions, of this medicinal plant were evaluated by Salmonella typhimurium assay, using strains TA100, TA98, TA102 and TA97a, and in mouse reticulocytes. The results showed mutagenic activity of the methanolic extract in the TA98 strain without S9, but no mutagenicity to mouse cells in any of the extracts. The acetate fraction showed strong signs of mutagenicity without S9, suggesting that in this enriched fraction were concentrated the compounds that induced mutagenic activity. The aqueous fraction showed no mutagenic activity. The TLC and HSCCC analyses of the acetate fraction with some standard compounds permitted the isolation of the quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, amentoflavone, methyl gallate and (+)-catechin, of which only the amentoflavone exhibited positive mutagenicity to TA98 (+S9, -S9).
Assuntos
Biflavonoides/toxicidade , Malpighiaceae/química , Salmonella typhimurium/efeitos dos fármacos , Animais , Catequina/toxicidade , Feminino , Galactosídeos/toxicidade , Ácido Gálico/análogos & derivados , Ácido Gálico/toxicidade , Glicosídeos/toxicidade , Masculino , Metanol/química , Camundongos , Testes para Micronúcleos , Mutação , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Quercetina/análogos & derivados , Quercetina/toxicidade , Salmonella typhimurium/genéticaRESUMO
The purpose of this study was to compare the basal cytotoxicity and metabolism-mediated cytotoxicity of kaempferol, quercetin and rutin. McCoy cells were exposed to various concentrations of the flavonols with and without the S9 system. The neutral red uptake assay was used to determine viability after 24 h at 35-37 degrees C. Dose-response curves were established for each flavonol in the presence and absence of external metabolizing systems. Kaempferol and quercetin were cytotoxic and provoked a dose-dependent decrease in cell viability, without the S9 system. The hepatic S9 microsomal fraction metabolized these compounds to less cytotoxic metabolites. In contrast, rutin at 500 microg/ml failed to produce any overt signs of toxicity in either assay.