RESUMO
Furanocoumarins are naturally occurring compounds in the plant world, characterized by low molecular weight, simple chemical structure, and high solubility in most organic solvents. Additionally, they have a broad spectrum of activity, and their properties depend on the location and type of attached substituents. Therefore, the aim of our study was to investigate the anticancer activity of furanocoumarins (imperatorin, isoimperatorin, bergapten, and xanthotoxin) in relation to human glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cell lines. The tested compounds were used for the first time in combination with LY294002 (PI3K inhibitor) and sorafenib (Raf inhibitor). Apoptosis, autophagy, and necrosis were identified microscopically after straining with Hoechst 33342, acridine orange, and propidium iodide, respectively. The levels of caspase 3 and Beclin 1 were estimated by immunoblotting and for the blocking of Raf and PI3K kinases, the transfection with specific siRNA was used. The scratch test was used to assess the migration potential of glioma cells. Our studies showed that the anticancer activity of furanocoumarins strictly depended on the presence, type, and location of substituents. The obtained results suggest that achieving higher pro-apoptotic activity is determined by the presence of an isoprenyl moiety at the C8 position of the coumarin skeleton. In both anaplastic astrocytoma and glioblastoma, imperatorin was the most effective in induction apoptosis. Furthermore, the usage of imperatorin, alone and in combination with sorafenib or LY294002, decreased the migratory potential of MOGGCCM and T98G cells.
Assuntos
Astrocitoma , Cromonas , Furocumarinas , Glioblastoma , Glioma , Morfolinas , Humanos , Sorafenibe/farmacologia , Fosfatidilinositol 3-Quinases , Glioma/tratamento farmacológico , Furocumarinas/farmacologiaRESUMO
BACKGROUND: Symphytum (comfrey) genus, particularly Symphytum officinale, has been empirically used in folk medicine mainly for its potent anti-inflammatory properties. In an attempt to shed light on the valorization of less known taxa, the current study evaluated the metabolite profile and antioxidant and enzyme inhibitory effects of nine Symphytum species. RESULTS: Phenolic acids, flavonoids and pyrrolizidine alkaloids were the most representative compounds in all comfrey samples. Hierarchical cluster analysis revealed that, within the roots, S. grandiflorum was slightly different from S. ibericum, S. caucasicum and the remaining species. Within the aerial parts, S. caucasicum and S. asperum differed from the other samples. All Symphytum species showed good antioxidant and enzyme inhibitory activities, as evaluated in DPPH (up to 50.17 mg Trolox equivalents (TE) g-1), ABTS (up to 49.92 mg TE g-1), cupric reducing antioxidant capacity (CUPRAC, up to 92.93 mg TE g-1), ferric reducing antioxidant power (FRAP, up to 53.63 mg TE g-1), acetylcholinesterase (AChE, up to 0.52 mg galanthamine equivalents (GALAE) g-1), butyrylcholinesterase (BChE, up to 0.96 mg GALAE g-1), tyrosinase (up to 13.58 mg kojic acid equivalents g-1) and glucosidase (up to 0.28 mmol acarbose equivalents g-1) tests. Pearson correlation analysis revealed potential links between danshensu and ABTS/FRAP/CUPRAC, quercetin-O-hexoside and DPPH/CUPRAC, or rabdosiin and anti-BChE activity. CONCLUSIONS: By assessing for the first time in a comparative manner the phytochemical-biological profile of a considerably high number of Symphytum samples, this study unveils the potential use of less common comfrey species as novel phytopharmaceutical or agricultural raw materials. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Antioxidantes , Benzotiazóis , Confrei , Ácidos Sulfônicos , Antioxidantes/química , Confrei/química , Butirilcolinesterase , Acetilcolinesterase , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologiaRESUMO
Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.
Assuntos
Anticonvulsivantes , Ácido Valproico , Animais , Camundongos , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/farmacocinética , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Eletrochoque , Interações Medicamentosas , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Fenobarbital/farmacologia , Fenobarbital/uso terapêutico , Encéfalo , Modelos Animais de Doenças , Relação Dose-Resposta a DrogaRESUMO
Hot Melt Extrusion (HME) technology was developed to obtain blends containing lyophilized Scutellariae baicalensis root extract and chitosan in order to improve the rheological properties of the obtained blends, including tableting and compressibility properties. (Hydroxypropyl)methyl cellulose (HPMC) in 3 different ratios was used as amorphous matrix formers. The systems were characterized using X-ray powder diffraction (PXRD), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), and in vitro release, permeability, and microbiological activity studies. Then, the extrudates were used to prepare tablets in order to give them the appropriate pharmaceutical form. HPMC-based systems released baicalin more slowly, resulting in delayed peaks in the acceptor fluid. This behavior can be explained by the fact that HPMC swells significantly, and the dissolved substance must have diffused through the polymer network before being released. The best tabletability properties are provided by the formulation containing the extrudate with lyophilized extract HPMC 50:50 w/w. These tablets offer a valuable baicalin release profile while maintaining good mucoadhesive properties that condition the tablet's retention in the application site and the effectiveness of therapy.
Assuntos
Química Farmacêutica , Quitosana , Química Farmacêutica/métodos , Tecnologia de Extrusão por Fusão a Quente , Solubilidade , Comprimidos , Composição de Medicamentos/métodos , Temperatura AltaRESUMO
Anxiety is one of the most common central nervous system disorders, affecting at least one-quarter of the worldwide population. The medications routinely used for the treatment of anxiety (mainly benzodiazepines) are a cause of addiction and are characterized by many undesirable side effects. Thus, there is an important and urgent need for screening and finding novel drug candidates that can be used in the prevention or treatment of anxiety. Simple coumarins usually do not show side effects, or these effects are much lower than in the case of synthetic drugs acting on the central nervous system (CNS). This study aimed to evaluate the anxiolytic activity of three simple coumarins from Peucedanum luxurians Tamamsch, namely officinalin, stenocarpin isobutyrate, and officinalin isobutyrate, in a 5 dpf larval zebrafish model. Moreover, the influence of the tested coumarins on the expression of genes involved in the neural activity (c-fos, bdnf) or dopaminergic (th1), serotoninergic (htr1Aa, htr1b, htr2b), GABA-ergic (gabarapa, gabarapb), enkephalinergic (penka, penkb), and galaninergic (galn) neurotransmission was assessed by quantitative PCR. All tested coumarins showed significant anxiolytic activity, with officinalin as the most potent compound. The presence of a free hydroxyl group at position C-7 and the lack of methoxy moiety at position C-8 might be key structural features responsible for the observed effects. In addition, officinalin and its isobutyrate upregulated the expression of genes involved in neurotransmission and decreased the expression of genes connected with neural activity. Therefore, the coumarins from P. luxurians might be considered as promising drug candidates for the therapy of anxiety and related disorders.
Assuntos
Ansiolíticos , Animais , Ansiolíticos/farmacologia , Peixe-Zebra/genética , Frutas/química , Isobutiratos/análise , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Cumarínicos/química , Expressão GênicaRESUMO
Epilepsy is a neurological disease that burdens over 50 million people worldwide. Despite the considerable number of available antiseizure medications, it is estimated that around 30% of patients still do not respond to available treatment. Herbal medicines represent a promising source of new antiseizure drugs. This study aimed to identify new drug lead candidates with antiseizure activity from endemic plants of New Caledonia. The crude methanolic leaf extract of Halfordia kendack Guillaumin (Rutaceae) significantly decreased (75 µg/mL and 100 µg/mL) seizure-like behaviour compared to sodium valproate in a zebrafish pentylenetetrazole (PTZ)-induced acute seizure model. The main coumarin compound, halfordin, was subsequently isolated by liquid-liquid chromatography and subjected to locomotor, local field potential (LFP), and gene expression assays. Halfordin (20 µM) significantly decreased convulsive-like behaviour in the locomotor and LFP analysis (by 41.4% and 60%, respectively) and significantly modulated galn, and penka gene expression.
Assuntos
Epilepsia , Pentilenotetrazol , Animais , Anticonvulsivantes/toxicidade , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Pentilenotetrazol/farmacologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Peixe-ZebraRESUMO
The large quantity of olive roots resulting from a large number of old and unfruitful trees encouraged us to look for ways of adding value to these roots. For this reason, the current research work is devoted to the valorization of olive roots by identifying active phytochemicals and assessing their biological activities, including the cytotoxicity and antiviral potential of different extracts from the Olea europaea Chemlali cultivar. The extract, obtained by ultrasonic extraction, was analyzed using the liquid chromatography-mass spectrometry technique (LC-MS). The cytotoxicity was evaluated through the use of the microculture tetrazolium assay (MTT) against VERO cells. Subsequently, the antiviral activity was determined for HHV-1 (Human Herpesvirus type 1) and CVB3 (Coxsackievirus B3) replication in the infected VERO cells. LC-MS analysis allowed the identification of 40 compounds, classified as secoiridoids (53%), organic acids (13%), iridoids (10%), lignans (8%), caffeoylphenylethanoid (5%), phenylethanoids (5%),sugars and derivatives (2%), phenolic acids (2%), and flavonoids (2%). It was found that extracts were not toxic to the VERO cells. Moreover, the extracts did not influence the appearance of HHV-1 or CVB3 cytopathic effects in the infected VERO cells and failed to decrease the viral infectious titer.
Assuntos
Olea , Chlorocebus aethiops , Animais , Humanos , Olea/química , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Células Vero , Cromatografia Líquida de Alta Pressão/métodos , Fenóis/química , Folhas de Planta/química , Cromatografia Líquida , Iridoides/química , Extratos Vegetais/química , Flavonoides/químicaRESUMO
Amaranth is used as a spinach replacement; therefore, it is sometimes called Chinese Spinach. So far, the activity of the plant has not been associated with the presence of specific compounds. Three cultivars of Amaranthus tricolor L. were investigated for their antioxidant and antimicrobial activities. The correlation between the bioactivity and metabolite profiles was investigated in order to indicate active compounds in A. tricolor. The phytochemical profile of a total of nine extracts was studied by HPLC-DAD-ESI/HRMS, revealing the presence of 52 compounds. The highest antioxidant activity was noticed in the Red cultivar (0.06 mmol TE/g DE (Trolox Equivalent/Dry Extract Weight) and was related to the presence of amino acids, flavonoids and phenolic acids, as well as individual compounds such as tuberonic acid hexoside. All studied extracts revealed antimicrobial activity. Gram-positive bacteria were more susceptible to N-(carboxyacetyl) phenylalanine, phenylalanine, tuberonic acid and succinic acid and Gram-negative bacteria to dopa, tryptophan, norleucine, tuberonic acid hexoside, quercetin-O-hexoside, luteolin-O-rhamnosylhexoside, luteolin-6-C-hexoside succinic acid, gallic acid-O-hexoside, dihydroxybenzoic acid and hydroxybenzoic acid. Maleic acid showed promising antifungal activity. In summary, A. tricolor is a good source of antioxidant and antimicrobial compounds.
Assuntos
Amaranthus , Anti-Infecciosos , Antioxidantes/análise , Verduras/metabolismo , Amaranthus/química , Luteolina/análise , Flavonoides/análise , Anti-Infecciosos/farmacologia , Anti-Infecciosos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Succinatos/análise , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
Peppers are among the spices possessing a wide plethora of biological properties due to their excellent supply of health-related metabolites. Capsicum annuum L. (Solanaceae) is cultivated throughout Tunisia, and there is a shortage of information on the identification of the secondary metabolites in the seeds of this species as well as on their biological activities. In the present work, we intended to undertake a chemical characterization of the bioactive compounds from the hydro-methanolic seed extract of C. annuum as well as an evaluation of its broad spectrum of antimicrobial and antioxidant activities. The chemical profile was evaluated by RP-HPLC-DAD-QTOF-MS/MS, whereas the total phenol and flavonoid content, antioxidant, and antimicrobial activities were determined in in vitro assays. In this work, 45 compounds belonging to various phytochemical classes, such as organic acids (2), phenolic compounds (4 phenolic acids and 5 flavonoids), capsaicinoids (3), capsianosides (5), fatty acids (13), amino acids (1), sphingolipids (10), and steroids (2) were identified in the hydro-methanolic seed extract of C. annuum. The phenolic and flavonoid content (193.7 mg GAE/g DW and 25.1 mg QE/g DW, respectively) of the C. annuum extract correlated with the high antiradical activity (IC50 = 45.0 µg/mL), reducing power (EC50 = 61.3 µg/mL) and chelating power (IC50 = 79.0 µg/mL) activities. The hydro-methanolic seed extract showed an important antimicrobial activity against seven bacterial and four fungal strains. In fact, the inhibition zones (IZs) for bacteria ranged from 9.00 ± 1.00 mm to 12.00 ± 0.00 mm; for fungi, the IZs ranged from 12.66 ± 0.57 mm to 13.66 ± 0.57 mm. The minimal inhibition concentration and minimal bactericidal concentration values showed that the extract was more effective against fungi than bacteria.
Assuntos
Capsicum , Antioxidantes/farmacologia , Espectrometria de Massas em Tandem , Fenóis/farmacologia , Flavonoides/farmacologia , Metanol , Extratos Vegetais/farmacologiaRESUMO
In this study a multi-residue determination method for 36 pesticides in dried hops was reported. The sample preparation procedure was based on the acetate buffered QuEChERS method. A few mixtures of dispersive solid phase extraction (dSPE) sorbents consisting PSA, C18, GCB, Z-Sep and Z-Sep+ were investigated to clean-up the supernatant and minimize matrix co-extractives. The degree of clean-up was assessed by gravimetric measurements, which showed the best results for mixtures containing the Z-Sep+ sorbent. This is the first study to apply Z-Sep+ sorbent for hops material and the first to improve the method for pesticide residues determination in hops. Samples were analysed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and the procedure was validated according to the SANTE/11813/2017 document at four concentration levels: 0.02, 0.05, 0.1 and 1 mg/kg. The limits of quantification (LOQ) were in the range of 0.02-0.1 mg/kg. For all active substances, the trueness (recovery) ranged from 70 to 120% and the precision (RSDr) value was <20%. Specificity, linearity and matrix effect were also evaluated. The validated method was applied to the analysis of 15 real dried hop samples and the relevant data on detected residues were included.
Assuntos
Humulus , Resíduos de Praguicidas , Praguicidas , Praguicidas/análise , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Resíduos de Praguicidas/análise , Extração em Fase Sólida/métodosRESUMO
Moringa oleifera Lam. is a perennial tropical deciduous tree with high economic and pharmaceutical value. As an edible plant, M. oleifera Lam. is rich in nutrients, such as proteins, amino acids, mineral elements and vitamins. Besides, it also contains an important number of bioactive phytochemicals, such as polysaccharides, flavonoids, alkaloids, glucosinolates and isothiocyanates. M. oleifera for long has been used as a natural anti-diabetic herb in India and other Asian countries. Thus, the anti-diabetic properties of Moringa plant have evolved highly attention to the researchers. In the last twenty years, a huge number of new chemical structures and their pharmacological activities have been reported in particularly the anti-diabetic properties. The current review highlighted the bioactive phytochemicals from M. Oleifera. Moreover, evidence regarding the therapeutic potential of M. oleifera for diabetes including experimental and clinical data was presented and the underlying mechanisms were revealed in order to provide insights for the development of novel drugs.
Assuntos
Diabetes Mellitus , Moringa oleifera , Antioxidantes/análise , Diabetes Mellitus/tratamento farmacológico , Humanos , Moringa oleifera/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91â µM, while the reference (galantamine) had IC50 =1.85±0.12â µM. Compounds 9 (IC50 75.14±1.82â µM), 13 (IC50 =16.14±0.43â µM), were determined to be stronger BChE inhibitors than the reference galantamine (IC50 =93.53±2.23â µM). The IC50 value of compound 16 for BChE inhibition (IC50 =126.56±11.96â µM) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.
Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Galantamina , Cumarínicos/farmacologia , Cumarínicos/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Doença de Alzheimer/tratamento farmacológico , Simulação de Acoplamento Molecular , Relação Estrutura-AtividadeRESUMO
Imperatorin, a naturally derived furanocoumarin, exerts promising neuropharmacological properties. Therefore, it might be applicable in the treatment of brain diseases such as depression. In the present project, we aimed to investigate the sex-dependent effects of imperatorin (1, 5, and 10 mg/kg) on behavior and neurochemistry associated with antidepressant effects. The depressive-like behaviors of male and female Swiss mice were investigated in a forced swim test (FST). Subsequently, High-Performance Liquid Chromatography (HPLC) was used to evaluate the level of serotonin, its metabolite, 5-HIAA, and noradrenaline, in mouse brains. The study revealed that only males responded to imperatorin (1 and 5 mg/kg) treatment and caused an antidepressant effect, such as with respect to depressive-like behaviors, lowering immobility time and increasing immobility latency. The HPLC analysis demonstrated that serotonin levels in the prefrontal cortex of females decreased with the middle dose of imperatorin (5 mg/kg), while in the male prefrontal cortex, the lower dose (1 mg/kg) boosted serotonin levels. There were no evident changes observed with respect to noradrenaline and serotonin metabolite levels in the male hippocampus. To conclude, we propose that imperatorin has antidepressant potential, seemingly only in males, influencing brain serotonin level, but the direct mechanism of action requires further investigation.
Assuntos
Comportamento Animal/efeitos dos fármacos , Depressão , Furocumarinas/farmacologia , Córtex Pré-Frontal , Caracteres Sexuais , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/fisiopatologia , Feminino , Furocumarinas/farmacocinética , Masculino , Camundongos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologiaRESUMO
Iphiona mucronata (Family Asteraceae) is widely distributed in the Eastern desert of Egypt. It is a promising plant material for phytochemical analysis and pharmacologic studies, and so far, its specific metabolites and biological activity have not yet been thoroughly investigated. Herein, we report on the detailed phytochemical study using UPLC-Q-TOF-MS approach. This analysis allowed the putative annotation of 48 metabolites belonging to various phytochemical classes, including mostly sesquiterpenes, flavonoids, and phenolic acids. Further, zebrafish embryotoxicity has been carried out, where 100 µg/mL extract incubated for 72 h resulted in a slow touch response of the 10 examined larvae, which might be taken as a sign of a disturbed peripheral nervous system. Results of in vitro testing indicate moderate cytotoxicity towards VERO, FaDu, and HeLa cells with CC50 values between 91.6 and 101.7 µg/mL. However, selective antineoplastic activity in RKO cells with CC50 of 54.5 µg/mL was observed. To the best of our knowledge, this is the first comprehensive profile of I. mucronata secondary metabolites that provides chemical-based evidence for its biological effects. A further investigation should be carried out to precisely define the underlying mechanisms of toxicity.
Assuntos
Asteraceae , Peixe-Zebra , Humanos , Animais , Células HeLa , Extratos Vegetais/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Y. schidigera contains a number of unusual polyphenols, derivatives of resveratrol and naringenin, called spiro-flavostilbenoids, which have potent in vitro anti-inflammatory, antioxidant, and moderate cholinesterase inhibitory activities. To date, these compounds have not been tested in vivo for the treatment of neurodegenerative diseases. The aim of the present study was to evaluate the effects of both single spiro-flavostilbenoids (yuccaol B and gloriosaol A) and phenolic fractions derived from Y. schidigera bark on scopolamine-induced anxiety and memory process deterioration using a Danio rerio model. Detailed phytochemical analysis of the studied fractions was carried out using different chromatographic techniques and Nuclear Magnetic Resonance (NMR). The novel tank diving test was used as a method to measure zebrafish anxiety, whereas spatial working memory function was assessed in Y-maze. In addition, acetylcholinesterase/butyrylcholinesterase (AChE/BChE) and 15-lipooxygenase (15-LOX) inhibition tests were performed in vitro. All pure compounds and fractions under study exerted anxiolytic and procognitive action. Moreover, strong anti-oxidant capacity was observed, whereas weak inhibition towards cholinesterases was found. Thus, we may conclude that the observed behavioral effects are complex and result rather from inhibition of oxidative stress processes and influence on cholinergic muscarinic receptors (both 15-LOX and scopolamine assays) than effects on cholinesterases. Y. schidigera is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.
Assuntos
Fármacos Neuroprotetores , Yucca , Acetilcolinesterase , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Butirilcolinesterase , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Fenóis/química , Casca de Planta/química , Extratos Vegetais/química , Escopolamina/efeitos adversos , Escopolamina/análise , Yucca/química , Peixe-ZebraRESUMO
The composition of the ethanolic extract from the aerial parts of Crocus alatavicus Regel & Semen from southern Kazakhstan spontaneous flora was analyzed together with the determination of its antibacterial, antifungal, antiviral and anticancer activity. The phytochemical profile analysis by high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (HPLC/ESI-QTOF-MS) revealed the presence of multiple kaempferol derivatives. High-performance reverse-phase liquid chromatography combined with a photodiode-array detection (RP-HPLC/PDA) found that kaempferol 3-O-dihexoside and kaempferol 3-O-acyltetrahexoside accounted for 70.5% of the kaempferol derivatives. The minimum inhibitory concentration (MIC) values of the extract for all the tested reference microorganisms were high, reaching 10 mg/mL for yeasts and 20 mg/mL for bacteria. In contrast, antiviral activity was observed at 2 mg/mL, resulting in the inhibition of the HSV-1-induced cytopathic effect and the reduction in virus infectious titer by 1.96 log, as well as the viral load by 0.85 log. Among the tested prostate cancer cell lines, significant cytotoxic activity of the extract was noted only on the LNCaP cell line, with an IC50 value of 1.95 mg/mL. The LNCaP cell line treated with 2 mg/mL of the extract showed a noticeably reduced number of spindle-shaped cells with longer cellular projections, a significant increase in the peak corresponding to the population of apoptotic cells in the sub-G1 phase and a decreased intracellular glutathione (GSH) level, suggesting the prooxidative properties of the extract. The obtained data provide novel information about the flavonoids present in the aerial part of C. alatavicus and suggest its potential application as a source of the compounds active against HSV-1 and metastatic, androgen-sensitive prostate cancer.
Assuntos
Crocus , Etanol , Extratos Vegetais , Sementes , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Etanol/química , Etanol/farmacologia , Humanos , Quempferóis/análise , Cazaquistão , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Sementes/química , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
INTRODUCTION: Symphytum officinale L. (comfrey, Boraginaceae) is a cultivated or spontaneously growing medicinal plant that is traditionally used for the treatment of bone fractures, hematomas, muscle pains and joint pains. A wide range of topical preparations and dried roots for ex tempore applications are marketed in European drug stores or pharmacies. OBJECTIVE: The aim of this study was to perform the qualitative and quantitative analysis of pyrrolizidine alkaloids (PAs) and phenolic compounds in the hydroethanolic extracts of 16 commercial comfrey root batches purchased from 12 different European countries. METHODS: Liquid chromatography hyphenated with high-resolution tandem mass spectrometry (LC-HRMS/MS) was used for the profiling of PAs and phenolic compounds, whereas LC-MS/MS and liquid chromatography with diode array detection (LC-DAD) were used for their quantification. RESULTS: 20 PAs (i.e. intermedine, lycopsamine, acetylintermedine, acetyllycopsamine, symphytine, symphytine-N-oxide), 17 phenolic compounds (i.e. caffeic and rosmarinic acids, rabdosiin, globoidnan A, globoidnan B) and 9 nonphenolic compounds (sugars, organic and fatty acids) were fully or partly annotated in the analysed samples. In addition, the quantitative analyses revealed that globoidnan B, rabdosiin and globoidnan A are new phenolic markers that can be used together with rosmarinic acid and PAs for the quality control of commercial comfrey root batches. CONCLUSIONS: This study brings new insights into the phytochemical complexity of S. officinale, revealing not only numerous toxic PAs, but also a significant number of valuable phenolic compounds that could contribute to the bioactivities of comfrey-based preparations.
Assuntos
Confrei , Alcaloides de Pirrolizidina , Ácidos Cafeicos , Cromatografia Líquida , Europa (Continente) , Lignanas , Extratos Vegetais , Raízes de Plantas , Espectrometria de Massas em TandemRESUMO
Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83-89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.
Assuntos
Anticonvulsivantes/farmacologia , Cumarínicos/farmacologia , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Peixe-Zebra/fisiologia , 4-Aminobutirato Transaminase/efeitos dos fármacos , Animais , Convulsivantes/farmacologia , Mesencéfalo/fisiologia , Pentilenotetrazol/farmacologia , Extratos Vegetais/farmacologia , Convulsões/prevenção & controleRESUMO
Neuroinflammation plays an essential role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Although coumarins have been shown to improve cognitive function in animal models and exert anti-inflammatory effects in cell cultures, the exact mechanism of their neuroprotective effects has not yet been fully elucidated. The present study aimed to investigate the neuroprotective effects of xanthotoxin (furanocoumarin) and umbelliferone (simple coumarin) in lipopolysaccharide-induced cognitive dysfunction in mice. For evaluation memory and learning processes, a passive avoidance test was used. Furthermore, acetylcholinesterase level and impact on the tumor necrosis factor α, interleukin 10 levels in the whole brain, and cyclooxygenase-II in hippocampus was established. Subchronic administration of both coumarins (15 mg/kg) enhanced the learning and memory function, but only the xanthotoxin improved cognitive processes impaired by lipopolysaccharide (0.8 mg/kg) administration. Behavioral results stay in line with acetylcholinesterase level in the brain. A statistically significant decrease in the level of tumor necrosis factor α and cyclooxygenase-II in lipopolysaccharide-treated rodents after coumarins' administration was observed. Together, our findings demonstrate that both coumarins improved cognitive functions, but only xanthotoxin significantly enhanced the learning and memory function and reduced the level of acetylcholinesterase in lipopolysaccharide-treated mice. This effect may suggest that only furanocoumarin-xanthotoxin attenuates neuroinflammation and enhances cholinergic neurotransmission, thus it can be a potential remedy with procognitive potential effective in treatment of neuroinflammatory disease.
Assuntos
Amnésia/tratamento farmacológico , Cognição/efeitos dos fármacos , Metoxaleno/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Umbeliferonas/uso terapêutico , Amnésia/induzido quimicamente , Animais , Lipopolissacarídeos , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , CamundongosRESUMO
Different types of anxiety disorders have become the number one mental health issue in developed countries. The search for new, safer and effective drug-like molecules among naturally derived substances faces two difficulties: an efficient method of isolation compounds with a high-purity and high-throughput animal model for activity assay. Thus, the aim of the present study was to isolate by liquid-liquid chromatography high-purity rare coumarins from the fruits of Seseli devenyense Simonk. and evaluate their anxiolytic effect (defined as reversed thimotaxis) using a 5-days post-fertilization (dpf) Danio rerio larvae model. Liquid-liquid chromatography enabled the isolation of one simple hydroxycoumarin (devenyol) and four pyranocoumarins (cis-khellactone, d-laserpitin, isolaserpitin and octanoyllomatin). The anxiolytic effect was defined as a decrease in the time spent in the boundaries of the living space (also described as reversed thigmotaxis). Our results show that all isolated courmarins exerted a significant influence on the anxiety behavior (anxiolytic activity) in the zebrafish larvae model. According to our knowledge, this is the first report of anxiolytic activity of pyranocoumarins and devenyol.