RESUMO
Walnut (Juglans regia L.) septum represents an interesting bioactive compound source by-product. In our study, a rich phenolic walnut septum extract, previously selected, was further examined. The tocopherol content determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed higher amounts of α-tocopherol compared to γ- and δ-tocopherols. Moreover, several biological activities were investigated. The in vitro inhibiting assessment against acetylcholinesterase, α-glucosidase, or lipase attested a real management potential in diabetes or obesity. The extract demonstrated very strong antimicrobial potential against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enteritidis. It also revealed moderate (36.08%) and strong (43.27%) antimutagenic inhibitory effects against TA 98 and TA 100 strains. The cytotoxicity of the extract was assessed on cancerous (A549, T47D-KBluc, MCF-7) and normal (human gingival fibroblasts (HGF)) cell lines. Flow cytometry measurements confirmed the cytotoxicity of the extract in the cancerous cell lines. Additionally, the extract demonstrated antioxidant activity on all four cell types, as well as anti-inflammatory activity by lowering the inflammatory cytokines (interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 ß (IL-1ß)) evaluated in HGF cells. To the best of our knowledge, most of the cellular model analyses were performed for the first time in this matrix. The results prove that walnut septum may be a potential phytochemical source for pharmaceutical and food industry.
Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Juglans/química , Nozes/química , Tocoferóis/análise , Anti-Inflamatórios/análise , Antioxidantes/análise , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores da Colinesterase/análise , Cromatografia Líquida , Inibidores de Glicosídeo Hidrolases/análise , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipase/antagonistas & inibidores , Extratos Vegetais/análise , Extratos Vegetais/química , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella enteritidis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Espectrometria de Massas em TandemRESUMO
Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities.
Assuntos
Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Ácido Clorogênico/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Quercetina/análogos & derivados , Solidago/química , Anti-Infecciosos/classificação , Anti-Infecciosos/farmacologia , Antioxidantes/classificação , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/crescimento & desenvolvimento , Clorofórmio/química , Ácido Clorogênico/farmacologia , Etanol/química , Flavonoides/classificação , Flavonoides/farmacologia , Metanol/química , Testes de Sensibilidade Microbiana , Fenóis/classificação , Fenóis/farmacologia , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to investigate the phytochemical profile (e.g. iridoids, polyphenolic compounds, phytosterols), as well as the biological potential (antioxidant, antibacterial, antifungal, anti-inflammatory properties) of two selected Ajuga species collected from different regions of Romanian spontaneous flora. The main compounds identified in A. reptans aerial parts extracts were 8-O-acetylharpagide, isoquercitrin and ß-sitosterol, whilst in A. genevensis were 8-O-acetylharpagide, luteolin and campesterol. The extracts were screened for their antioxidant potential using different methods (DPPH, TEAC, EPR) and the results showed a good activity, in accordance with the polyphenol content (18-26 mg GAE/g dw). The antifungal activity on the tested strains was good. The determination of few parameters linked with the inflammatory mechanism allowed the assessment of in vivo anti-inflammatory potential. Ajuga reptans and A. genevensis ethanol extracts had anti-inflammatory activity through lowering the oxidative stress, phagocytosis, PMN and total leukocytes. The best anti-oxidative and anti-inflammatory activity was observed for the Ajuga reptans 100 mg dw/mL extract when compared with diclofenac, thus the dose could be correlated with the pharmacological effect. These findings provide substantial evidence that both selected Ajuga species have the potential to be valued as sources of phytochemicals in effective anti-inflammatory herbal preparations.
Assuntos
Ajuga/química , Iridoides/farmacologia , Fitosteróis/farmacologia , Fitoterapia/métodos , Polifenóis/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Inflamação/tratamento farmacológico , Iridoides/química , Iridoides/isolamento & purificação , Testes de Sensibilidade Microbiana , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fitosteróis/química , Fitosteróis/isolamento & purificação , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Plantas Medicinais , Polifenóis/química , Polifenóis/isolamento & purificação , Ratos , Ratos Wistar , RomêniaRESUMO
BACKGROUND: Although Galanthus nivalis L. (snowdrop) is known for the galanthamine content, used in the treatment of Alzheimer disease, the polyphenolic compounds of Amaryllidaceae species are less studied. Proper understanding of the polyphenolics in these extracts and of their antioxidant and antimicrobial properties may allow a reconsideration of their medicinal uses. METHODS: The polyphenolic content of four selected Amaryllidaceae species harvested from Romania (Galanthus nivalis L., Narcissus pseudonarcissus L., N. poeticus L. and Leucojum vernum L.) was determined by spectrophotometric methods; the identification of phenolic compounds was performed by a HPLC-MS method, in order to establish their polyphenolic fingerprints. For the evaluation of the antioxidant potential the following methods were employed: DPPH radical scavenging, FRAP, hemoglobin ascorbate peroxidase activity inhibition (HAPX), inhibition of lipid peroxidation catalyzed by cytochrome c, and electron paramagnetic resonance (EPR) spectroscopy assays. Antimicrobial activity was assessed using the disc diffusion method. RESULTS: Qualitative and quantitative analyses highlight important amount of polyphenols (over 15 mg/g); the main identified compounds are chlorogenic and p-coumaric acids in all species. Only G. nivalis shows antioxidant activity by all the used methods. G. nivalis and L. vernum strongly inhibits the growth of S. aureus, while N. poeticus shows a very good antifungal activity. CONCLUSIONS: The results of this study provide a new approach to the properties and therapeutic uses of some Romanian widespread Amaryllidaceae species that could be considered sources of developing new medicinal products with anti anti-staphylococcal and antifungal activity.
Assuntos
Amaryllidaceae/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo , Peroxidação de Lipídeos/efeitos dos fármacos , Picratos , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia , RomêniaRESUMO
Plant by-products can be valuable sources of polyphenol bioactive compounds. Walnut (Juglans regia L.) is a very important tree nut rich in biologically active molecules, but its septum was scarcely researched. Experimental data indicated a hypoglycemic effect of septum extracts, with almost no details about its phytochemical composition. The main objectives of this study were: (1) to obtain walnut septum (WS) extracts with high content in bioactive compounds and antioxidant activity based on an original experimental design; (2) characterization of the phytochemical profile of the WS extracts using HPLC-MS/MS; (3) evaluation of the biological potential of the richest polyphenolic WS extract. The variables of the experimental design were: extraction method (maceration and Ultra-Turrax extraction), temperature, solvent (acetone and ethanol), and percentage of water in the solvent. The first quantifiable responses were: total phenolic content, total flavonoid content, condensed tannins, and ABTS antioxidant capacity. The phytochemical profile of lyophilized extracts obtained by Ultra-Turrax extraction (UTE), the most efficient method, was further determined by HPLC-MS/MS analysis of individual polyphenolic and phytosterols compounds. It is the first study to assay the detailed composition of WS in hydrophilic and lipophilic compounds. The biological potential of the richest polyphenolic WS extract was also evaluated by FRAP and DPPH antioxidant capacity and the inhibition of tyrosinase, an enzyme involved in the browning in fruits and vegetables, skin wrinkles and aging. Conclusion: The phytochemical profile of the analyzed extracts proves that WS can be a valuable source of biologically active compounds (polyphenols) for food and/or pharmaceutical industry and warrant the continuation of current research in further evaluating its bioactive potential.
Assuntos
Flavonoides/química , Juglans/química , Compostos Fitoquímicos/química , Polifenóis/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Humanos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Solventes/química , Espectrometria de Massas em TandemRESUMO
Antennaria dioica (L.) Gaertn. and Helichrysum arenarium (L.) Moench. are two species of the Asteraceae family, known in Romanian traditional medicine for their diuretic, choleretic, and anti-inflammatory properties. The aim of the present study was to evaluate the phenolic and sterolic composition of flowers from the two species and to assess their antioxidant, antibacterial and antifungal properties. LC-MS analyses were performed on methanolic, ethanolic and 70% v/v ethanolic extracts, before and after acid hydrolysis, and revealed high amounts of polyphenols. Chlorogenic acid was found as the main compound for the flowers of A. dioica (502.70 ± 25.11 mg/100 g d.w.), while quercitrin was dominant in H. arenarium (424.28 ± 21.21 mg/100 g d.w.) in 70% v/v ethanolic extracts before hydrolysis. Antioxidant capacity assays showed an important antioxidant potential, which can be correlated with the determined polyphenolic compounds, showing the 70% v/v ethanolic extracts of the two species as being the most effective antioxidant samples for the DPPH assay. Antibacterial and antifungal assays confirm a modest biological potential for the same extract of both species. Results obtained in the present study bring important data and offer scientific evidence on the chemical composition and on the biological activities of the flowers belonging to the two species.
Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Asteraceae/química , Flores/química , Helichrysum/química , Compostos Fitoquímicos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Ácido Clorogênico/química , Ácido Clorogênico/isolamento & purificação , Ácido Clorogênico/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Extração Líquido-Líquido/métodos , Penicillium/efeitos dos fármacos , Penicillium/crescimento & desenvolvimento , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitosteróis/química , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Extratos Vegetais/química , Quercetina/análogos & derivados , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Solventes/químicaRESUMO
Echinocystis lobata (Michx.) Torr. et A.Gray is a spontaneous species in the Romanian flora, lesser studied by scientific literature, but which has proved significant activities in traditional medicine. The present study is aimed to provide data on the polyphenolic compounds in the composition of the flowers of this species and to test their biological potential. Polyphenols were identified and quantified using an HPLC-MS method. Tested biological activities were the cytotoxic, anti-plasmodial and antioxidant ones. Methods used for testing the antioxidant activity were the DPPH, CUPRAC, FRAP, TEAC, EPR and SNPAC assays. Cytotoxic activity was tested on cancerous and healthy cell lines and anti-plasmodial activity was assesed on two strains of Plasmodium falciparum. Ethanolic extracts of the flowers of E. lobata proved to contain isoquercitrin, rutin, quercitrin, kaempferol, p-coumaric and ferulic acid. No cytotoxic and anti-plasmodial activity was found, but antioxidant assays showed an important antioxidant capacity. The obtained results show that flowers of E. lobata are important sources of antioxidant compounds. It is the first approach of the kind on the flowers of this species and it offers a new perspective on possible sources of antioxidant compounds.
Assuntos
Antioxidantes/análise , Cucurbitaceae/química , Polifenóis/análise , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Flores/química , Humanos , Espectrometria de Massas , Plasmodium falciparum/efeitos dos fármacosRESUMO
PURPOSE: To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. METHODS: This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. RESULTS: Fluvoxamine pretreatment increased Cmax and AUC0-∞ of nebivolol (Cmax: 1.67 ± 0.690 vs 2.20 ± 0.970 ng/mL; AUC0-∞: 12.1 ± 11.0 vs 19.3 ± 19.5 ng*h/mL ) and of its active metabolite (Cmax: 0.680 ± 0.220 vs 0.960 ± 0.290 ng/mL; AUC0-∞: 17.6 ±20.1 vs 25.5 ± 29.9 ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. CONCLUSIONS: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Assuntos
Fluvoxamina/farmacocinética , Nebivolol/farmacocinética , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Fluvoxamina/administração & dosagem , Fluvoxamina/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Nebivolol/administração & dosagem , Nebivolol/metabolismo , Adulto JovemRESUMO
BACKGROUND/AIMS: The effects of multiple-dose bupropion on the pharmacokinetics of single-dose carvedilol were investigated in order to evaluate this possible drug-drug interaction. METHODS: A preclinical study was conducted among white male Wistar rats. Each rat was cannulated on the femoral vein prior to being connected to BASi Culex ABC®. During the reference period, each rat received an intravenous and an oral dose of 3.57 mg/kg body weight (b.w.) carvedilol, at 2 days distance. After 5 days of pretreatment with 21.42 mg/kg b.w. bupropion (by oral route, twice a day - given in order to reach the steady state), during the sixth day, 3.57 mg/kg b.w. carvedilol and 21.42 mg/kg b.w. bupropion were orally co-administrated (test period). After each administration of carvedilol, several samples of 200 µL blood were collected. The pharmacokinetic parameters of carvedilol were analyzed by the noncompartmental method. RESULTS: The 5 days pretreatment with bupropion increased the exposure to carvedilol in rats by 180%, considering the modifications observed in the area under the curve of carvedilol. Carvedilol was shown to have higher plasma concentrations, delay in maximum concentration, and a prolonged half-life, after being pretreated with bupropion. CONCLUSION: The administration of multiple-dose bupropion influences the pharmacokinetics of carvedilol (single oral dose) in rats.
Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Bupropiona/farmacocinética , Carbazóis/farmacocinética , Inibidores da Captação de Dopamina/farmacocinética , Propanolaminas/farmacocinética , Animais , Carvedilol , Interações Medicamentosas/fisiologia , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND/AIMS: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). METHODS: Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. RESULTS: The results revealed significant differences between the study periods for Cmax, AUC0-t and AUC0-∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. CONCLUSION: FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies.
Assuntos
Inibidores da Captação Adrenérgica/farmacocinética , Antidepressivos/farmacocinética , Cloridrato de Atomoxetina/farmacocinética , Fluvoxamina/farmacocinética , Adolescente , Inibidores da Captação Adrenérgica/administração & dosagem , Adulto , Antidepressivos/administração & dosagem , Cloridrato de Atomoxetina/administração & dosagem , Interações Medicamentosas/fisiologia , Quimioterapia Combinada , Feminino , Fluvoxamina/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND/AIMS: The aim of this study was to investigate the drug-drug interaction between carvedilol and citalopram based on carvedilol metabolism in vitro and his pharmacokinetics (PKs) in vivo after the oral administration of the single drug and both drugs, and reveal citalopram effects on the PKs of carvedilol. METHODS: Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body weight [b.w.]) in the absence of citalopram or after a pre-treatment with multiple oral doses of citalopram (1.42 mg/kg b.w.). Plasma concentrations of carvedilol were determined using high-performance liquid chromatography-MS at the designated time points after drug administration, and the main PK parameters were calculated by noncompartmental analysis. In addition, effects of citalopram on the metabolic rate of carvedilol were investigated using rat-pooled liver microsome incubation systems. RESULTS: During co-administration, significant increases of the area under the plasma concentration-time curve as well as of the peak plasma concentration were observed. The rat-pooled liver microsome incubation experiment indicated that citalopram could decrease the metabolic rate of carvedilol. CONCLUSION: Citalopram co-administration led to a significant alteration of carvedilol's PK profile in rats; it also demonstrated, in vitro, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.
Assuntos
Carbazóis/farmacocinética , Citalopram/farmacologia , Propanolaminas/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Carvedilol , Cromatografia Líquida de Alta Pressão/métodos , Interações Medicamentosas/fisiologia , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem/métodosRESUMO
Romanian traditional medicine describes the use of aerial parts of Fumaria species to treat hepatobiliary diseases as well as diuretic agents. The present study aims to investigate the chemical composition, antioxidant properties, and diuretic effects of several Fumaria species. LC/MS analysis revealed that Fumaria species contain phenolic acids and high amounts of flavonoids with rutin and isoquercitrin as main compounds. Concerning antioxidant capacity, the most significant results were obtained for F. capreolata and F. vailantii. Both species showed a good correlation between the antioxidant capacity and a high amount of flavonoids. Furthermore, the extracts of F. officinalis and F. schleicheri produced a strong increase in urinary volumetric excretion of saline-loaded rats, 24 h after the oral administration of a single dose of 250 mg/kg bw. Moreover, both extracts of F. officinalis and F. schleicheri increased the urinary excretion of Na⺠and Kâº. Results from the present study offer a new perspective concerning the chemical composition and bioactivities of traditionally used fumitory species.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Diuréticos/química , Diuréticos/farmacologia , Fumaria/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Animais , Antioxidantes/administração & dosagem , Cromatografia Líquida de Alta Pressão , Diuréticos/administração & dosagem , Flavonoides/química , Masculino , Compostos Fitoquímicos/química , Extratos Vegetais/administração & dosagem , Ratos , Espectrometria de Massas em TandemRESUMO
The 50% ethanol extract obtained from Hedera helix leaves was investigated regarding the presence and quantity of polyphenols, sterols and in vitro antifungal activity against phytopathogenic fungi. The chemical analysis revealed the presence of rutin, quercetin and kaempferol in the non-hydrolysed sample and quercetin and kaempferol in the hydrolysed sample and stigmasterol in the ivy leaf extract (nonhydrolysed sample). The antifungal activity against phytopathogenic fungi (Aspergillus niger, Botrytis cinerea, B. tulipae, Fusarium oxysporum f. sp. tulipae, Penicillium gladioli, and Sclerotinia sclerotiorum) was assessed using an agar dilution assay. The results are expressed as the minimum inhibitory concentration (MIC = 10-14%) and were compared to a synthetic antifungal drug - fluconazole (MIC = 8-30%). This report presents the first screening of the antifungal activity of the ivy leaf extract on these plant pathogenic fungi species, aiming to use the ivy leaf extract for controlling different diseases of vegetables and ornamental plants, in addition to human disorders.
Assuntos
Antifúngicos/farmacologia , Fungos/crescimento & desenvolvimento , Hedera/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antifúngicos/química , Relação Dose-Resposta a Droga , Etanol/química , Extratos Vegetais/químicaRESUMO
PURPOSE: To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. METHODS: An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods. RESULTS: Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞ were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively. CONCLUSIONS: These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Assuntos
Cloridrato de Atomoxetina/química , Cloridrato de Atomoxetina/metabolismo , Bupropiona/química , Bupropiona/metabolismo , Adolescente , Adulto , Cloridrato de Atomoxetina/farmacocinética , Bupropiona/farmacocinética , Interações Medicamentosas , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND/AIMS: The study aimed at investigating the effects of multiple-dose bupropion (potent inhibitor of CYP2D6) on the pharmacokinetics (PKs) of single-dose nebivolol (CYP2D6 substrate) and to evaluate the clinical relevance of this potential drug interaction. METHODS: This open-label, nonrandomized clinical study had a 2-period design: during period 1 (reference), a single dose of 5 mg nebivolol was administered, while during period 2 (test), 5 mg nebivolol + 300 mg bupropion were ingested concomitantly, after a pretreatment regimen with bupropion (7 days). The PK parameters of nebivolol and its active metabolite were analyzed by noncompartmental modeling, while the pharmacodynamic (PD) parameters (blood pressure and heart rate) were assessed at rest. RESULTS: Bupropion plus nebivolol increased the mean peak plasma concentrations (Cmax) of nebivolol (1.67 ± 0.69 vs. 3.80 ± 1.70 ng/ml) and its active metabolite (0.68 ± 0.22 vs. 1.13 ± 0.38 ng/ml) compared to nebivolol alone. After bupropion pretreatment, the exposure to nebivolol was increased by 7.2-fold for the parent drug and 4-fold for the hydroxylated active metabolite. The difference between the PD parameters measured during the 2 periods was not significant. CONCLUSION: The study concluded that bupropion influenced the PKs of nebivolol in healthy volunteers, but a clinical relevance was not established. However, this latter aspect requires further investigation.
Assuntos
Antidepressivos de Segunda Geração/farmacocinética , Anti-Hipertensivos/farmacocinética , Bupropiona/farmacocinética , Nebivolol/farmacocinética , Adulto , Antidepressivos de Segunda Geração/sangue , Anti-Hipertensivos/sangue , Bupropiona/sangue , Interações Medicamentosas/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Nebivolol/sangue , Estudos Prospectivos , Adulto JovemRESUMO
Aerial parts of Veronica species are used in Romanian traditional medicine for the treatment of various conditions like kidney diseases, cough, and catarrh, and are known for their wound-healing properties. In the present study, the phenolic and sterolic content and the antioxidant and antimicrobial activities of three Veronica species (Plantaginaceae), V. officinalis L., V. teucrium L. and V. orchidea Crantz, were studied. The identification and quantification of several phenolic compounds and phytosterols were performed using LC/MS techniques and the main components were p-coumaric acid, ferulic acid, luteoline, hispidulin and ß-sitosterol. More than that, hispidulin, eupatorin and eupatilin were detected for the first time in the Veronica genus. Nevertheless, representatives of the Veronica genus were never investigated in terms of their phytosterol content. The antioxidant potential investigated by Trolox equivelents antioxidant capacity (TEAC) and EPR spectroscopy revealed that V. officinalis and V. orchidea extracts presented similar antioxidant capacities, whilst the values registered for V. teucrium extract are lower. Regarding the antimicrobial activity of the investigated species, Staphylococcus aureus, Listeria monocytogenes and Listeria ivanovii were the most sensitive strains with MIC values between 3.9 and 15.62 mg/mL. The results obtained by this study may serve to promote better use of representatives from the genus Veronica as antioxidant and antimicrobial agents.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/análise , Veronica/química , Anti-Infecciosos/química , Antioxidantes/química , Listeria/efeitos dos fármacos , Medicina Tradicional , Fenóis/análise , Fenóis/isolamento & purificação , Fenóis/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitosteróis/análise , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Veronica/classificaçãoRESUMO
L. barbarum L. is a widely-accepted nutraceutical presenting highly advantageous nutritive and antioxidant properties. Its flowers have been previously described as a source of diosgenin, ß-sitosterol and lanosterol that can be further pharmaceutically developed, but no other data regarding their composition is available. The purpose of this work was to investigate the chemical constituents, antioxidant and antimicrobial activities of L. barbarum flowers, as an alternative resource of naturally-occurring antioxidant compounds. The free radical scavenging activity of the ethanolic extract was tested by TEAC, two enzymatic assays with more physiological relevance and EPR spectroscopy. The presence of several phenolic compounds, such as chlorogenic, p-coumaric and ferulic acids, but also isoquercitrin, rutin and quercitrin, was assessed by an HPLC/MS method. The antioxidant assays revealed that the extract exhibited a moderate antioxidant potential. The antimicrobial activity was mild against Gram-positive bacteria and lacking against Escherichia coli. These findings complete the scarce existing data and offer new perspectives for further pharmaceutical valorization of L. barbarum flowers.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Flores/química , Lycium/química , Fenóis/farmacologia , Bacillus subtilis/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citocromos c/metabolismo , Flavonoides/análise , Sequestradores de Radicais Livres/farmacologia , Cinética , Lipossomos/química , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Oxirredução , Polifenóis/análiseRESUMO
This study was performed to evaluate the in vitro antimicrobial and antioxidant activities and the phenolic profile of Eucalytus globulus Labill. and Corymbia ficifolia (F. Muell.) K.D. Hill & L.A.S. Johnson leaves. Both leave extracts contain significant amounts of phenolic compounds, mainly flavonoids. Qualitative and quantitative analyses of the phenolic compounds were performed using a HPLC/MS method. The main flavonoid was hyperoside and its highest amount was found in E. globulus (666.42 ± 5.02 µg/g dw plant material). Regarding the flavonol profile, myricetin was the dominant compound and its highest amount was found in C. ficifolia leaves (124.46 ± 0.24 µg/g dw plant material). The antioxidant activity was evaluated by DPPH, TEAC, hemoglobin ascorbate peroxidase activity inhibition (HAPX) and inhibition of lipid peroxidation catalyzed by cytochrome c assays, revealing an important antioxidant potential for both species. In the antimicrobial assays, C. ficifolia extract was found to be more active than E. globulus against both Gram-positive and Gram-negative bacterial strains with the exception of Bacillus subtilis. The results of the present study provide new valuable data regarding the bioactivities of these medicinal species.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Myrtaceae/química , Polifenóis/química , Polifenóis/farmacologia , Bactérias/efeitos dos fármacos , Eucalyptus/química , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Myrtaceae/classificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais/químicaRESUMO
The purpose of this research was to bring new data regarding the phenolic composition and the antioxidant activity of L. barbarum L. and L. chinense Mill. leaves. The determination of the main polyphenolic compounds was performed using a HPLC-UV-MS method. The dominant compound found for both species was rutin, with its highest amount registered in L. chinense (24141.90±21.3 µ/g plant material) leaves. Among the flavonoidic aglycones, quercetin was found in both samples, being quantified in a higher amount in L. chinense. In the antioxidant assays, both extracts exhibited important antioxidant activities, as witnessed by the three methods, both correlated with their total polyphenolic content.
Assuntos
Antioxidantes/farmacologia , Lycium/química , Extratos Vegetais/farmacologia , Polifenóis/análise , Cromatografia Líquida de Alta Pressão , Folhas de Planta/químicaRESUMO
The aim of this paper was to evaluate the antioxidant and antimicrobial activities and the polyphenolic content of Schisandra chinensis (Turcz.) Baill. leaves and fruits. The leaves are an important source of flavonoids (35.10 ± 1.23 mg RE/g plant material). Qualitative and quantitative analyses of the polyphenolic compounds were achieved using a HPLC-UV-MS method. The main flavonoid from the leaves was isoquercitrin (2486.18 ± 5.72 µg/g plant material), followed by quercitrin (1645.14 ± 2.12 µg/g plant material). Regarding the fruit composition, the dominant compound there was rutin (13.02 ± 0.21 µg/g plant material), but comparing with the leaves, fruits can be considered a poor source of phenolic compounds. The antioxidant activity was evaluated by DPPH, TEAC, hemoglobin ascorbate peroxidase activity inhibition (HAPX), inhibition of lipid peroxidation catalyzed by cytochrome c and EPR spectroscopic assays, revealing a better antioxidant activity for the S. chinensis leaves extract. In the antimicrobial assay, S. chinensis leaves extract showed efficient activities against the targeted bacteria, being more active than the fruits extract. The results suggest the leaves of S. chinensis as a valuable source of antioxidant compounds with significant antioxidant activity.