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1.
Phytother Res ; 29(4): 526-32, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25644491

RESUMEN

Plant extracts have traditionally been used as sources of natural antimicrobial compounds, although in many cases, the compounds responsible for their antimicrobial efficacy have not been identified. In this study, crude and dialysed extracts from dandelion root (Taraxacum officinale) were evaluated for their antimicrobial properties against Gram positive and Gram negative bacterial strains. The methanol hydrophobic crude extract (DRE3) demonstrated the strongest inhibition of microbial growth against Staphylococcus aureus, methicillin-resistant S. aureus and Bacillus cereus strains. Normal phase (NP) fractionation of DRE3 resulted in two fractions (NPF4 and NPF5) with enhanced antimicrobial activity. Further NP fractionation of NPF4 resulted in two fractions (NPF403 and NPF406) with increased antimicrobial activity. Further isolation and characterisation of compounds in NPF406 using liquid chromatography solid phase extraction nuclear magnetic resonance LC-SPE-NMR resulted in the identification of 9-hydroxyoctadecatrienoic acid and 9-hydroxyoctadecadienoic acid, while the phenolic compounds vanillin, coniferaldehyde and p-methoxyphenylglyoxylic acid were also identified respectively. The molecular mass of these compounds was confirmed by LC mass spectroscopy (MS)/MS. In summary, the antimicrobial efficacy of dandelion root extracts demonstrated in this study support the use of dandelion root as a source of natural antimicrobial compounds.


Asunto(s)
Antibacterianos/farmacología , Bacillus cereus/efectos de los fármacos , Extractos Vegetales/farmacología , Staphylococcus aureus/efectos de los fármacos , Taraxacum/química , Cromatografía Liquida , Espectroscopía de Resonancia Magnética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Fenoles/química , Extractos Vegetales/química , Raíces de Plantas/química , Espectrometría de Masas en Tándem
2.
J Endocrinol ; 229(3): 319-30, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27098830

RESUMEN

Ablation of glucagon receptor signaling represents a potential treatment option for type 2 diabetes (T2DM). Additionally, activation of glucose-dependent insulinotropic polypeptide (GIP) receptor signaling also holds therapeutic promise for T2DM. Therefore, this study examined both independent and combined metabolic actions of desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon (glucagon receptor antagonist) and d-Ala(2)GIP (GIP receptor agonist) in diet-induced obese mice. Glucagon receptor binding has been linked to alpha-helical structure and desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon displayed enhanced alpha-helical content compared with native glucagon. In clonal pancreatic BRIN-BD11 beta-cells, desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon was devoid of any insulinotropic or cAMP-generating actions, and did not impede d-Ala(2)GIP-mediated (P<0.01 to P<0.001) effects on insulin and cAMP production. Twice-daily injection of desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon or d-Ala(2)GIP alone, and in combination, in high-fat-fed mice failed to affect body weight or energy intake. Circulating blood glucose levels were significantly (P<0.05 to P<0.01) decreased by all treatments regimens, with plasma and pancreatic insulin elevated (P<0.05 to P<0.001) in all mice receiving d-Ala(2)GIP. Interestingly, plasma glucagon concentrations were decreased (P<0.05) by sustained glucagon inhibition (day 28), but increased (P<0.05) by d-Ala(2)GIP therapy, with a combined treatment resulting in glucagon concentration similar to saline controls. All treatments improved (P<0.01) intraperitoneal and oral glucose tolerance, and peripheral insulin sensitivity. d-Ala(2)GIP-treated mice showed increased glucose-induced insulin secretion in response to intraperitoneal and oral glucose. Metabolic rate and ambulatory locomotor activity were increased (P<0.05 to P<0.001) in all desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon-treated mice. These studies highlight the potential of glucagon receptor inhibition alone, and in combination with GIP receptor activation, for T2DM treatment.


Asunto(s)
Polipéptido Inhibidor Gástrico/agonistas , Obesidad/tratamiento farmacológico , Receptores de Glucagón/antagonistas & inhibidores , Animales , Línea Celular , AMP Cíclico/biosíntesis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/efectos de los fármacos , Polipéptido Inhibidor Gástrico/administración & dosificación , Polipéptido Inhibidor Gástrico/análogos & derivados , Glucagón/administración & dosificación , Glucagón/análogos & derivados , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Masculino , Ratones , Ratones Obesos , Actividad Motora/efectos de los fármacos , Obesidad/etiología , Obesidad/fisiopatología , Ratas
3.
FEBS Lett ; 425(2): 234-8, 1998 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-9559655

RESUMEN

To understand the basic structural requirements for the biological activity of endothelin peptides, the solution structure of an ETB selective agonist, ET-1[Cys-(Acm)1,15, Ala3,Leu7,Aib11, was investigated by 1H NMR spectroscopy and molecular modelling. The structure is characterised by an alpha-helical conformation between residues Ser5-His16 but is undefined at both the N and C termini. To date, neither the solution structures of linear modified peptides nor the effects of a methanol/water solvent system have been examined for endothelin or endothelin-like peptides. This structure plays an important role towards the design of endothelin receptor selective agonists and antagonists.


Asunto(s)
Compuestos de Cadmio , Endotelina-1/análogos & derivados , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular/métodos , Estructura Secundaria de Proteína , Receptores de Endotelina/agonistas , Agua , Secuencia de Aminoácidos , Endotelina-1/química , Datos de Secuencia Molecular , Receptor de Endotelina B , Soluciones , Temperatura
4.
Neurochem Int ; 35(1): 35-45, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10403428

RESUMEN

Two-dimensional nuclear magnetic resonance techniques and a combination of distance geometry and molecular dynamics calculations were utilised to determine the three dimensional solution structure of an ET-1 analogue, ET-1[Aib1,3,11,15, Nle7], in a methanol-d3/water co-solvent. The modelled structure shows that the peptide folds into a consistent alpha-helical conformation between residues Ser4-His16 while the C-terminus prefers no fixed conformation. Our studies confirm that the disulphide links which are normally associated with the endothelin family of neuropeptides are not important for the formation of a helical conformation in solution. This full length, modified, synthetic linear ET-1 analogue plays a vital role towards designing endothelin receptor agonists. Structure activity relationships are discussed in terms of the conformational features of the calculated structure.


Asunto(s)
Endotelina-1/química , Secuencia de Aminoácidos , Gráficos por Computador , Disulfuros , Endotelina-1/análogos & derivados , Histidina , Modelos Moleculares , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular/métodos , Estructura Secundaria de Proteína , Serina , Programas Informáticos , Soluciones
5.
Phytochemistry ; 49(7): 1879-90, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9883588

RESUMEN

Three representatives of a novel class of amide (isopeptide) glycoconjugates have been synthesised: N alpha-D-galacturonoyl-L-lysine and N epsilon-D-galacturonoyl-L-lysine and N epsilon-D-polygalacturonoyl-L-lysine. Galacturonoyl-lysine amide bonds were labile in 2 M trifluoroacetic acid at 120 degrees and in alkali, but relatively stable in cold acid. The amide bonds were resistant to digestion by Driselase, Pronase and trypsin. The polysaccharide backbone of N epsilon-D-polygalacturonoyl-L-lysine was hydrolysed by Driselase to yield two major ninhydrin-positive compounds which were shown by 1H and 13C NMR spectroscopy to be tri- and tetra-alpha-(1-->4)-D-galacturonoyl-L-lysines. To investigate the possible natural occurrence of N-galacturonoyl isopeptide bonds, we fed cell-suspension cultures of spinach and tomato with D-[6-14C]glucuronic acid, which radio-labels pectic polysaccharides. The radioactive cell walls were digested with, sequentially, Driselase, mild acid, and proteinases. On electrophoresis at pH 2.0, several of the radioactive digestion-products were cathodic. Some of the cathodic products yielded [14C]galacturonic acid upon complete acid hydrolysis. The existence of these products is compatible with the presence of novel N-galacturonoyl isopeptide bonds, which could serve as cross-links in plant cell walls.


Asunto(s)
Amidas/síntesis química , Glicoconjugados/síntesis química , Ácidos Hexurónicos/síntesis química , Lisina/análogos & derivados , Solanum lycopersicum/metabolismo , Spinacia oleracea/metabolismo , Amidas/metabolismo , Secuencia de Carbohidratos , Pared Celular/metabolismo , Glicoconjugados/metabolismo , Ácidos Hexurónicos/metabolismo , Lisina/metabolismo , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular
6.
J Biomol Struct Dyn ; 16(2): 425-35, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9833679

RESUMEN

The solution structure of a synthetic ET(B) selective agonist, ET-1[Cys(Acm)(1,15), Ala3, Leu7, dAsp8, Aib11] has been solved by 1H NMR and molecular modelling studies. Such solution structures of linear modified peptides in aqueous methanol are being used in an ongoing program of research designed to assist in an understanding of the basic structural requirements for the biological activity of vasoconstrictors. The resulting structure of this peptide is characterised by an alpha-helical conformation between residues Leu6-His16 and by N- and C-termini which assume no defined conformation. A knowledge of the solution structures of this and related peptides, which are ET(B) selective agonists, are proving to be important in the understanding of how they interact with the ET(B) receptor.


Asunto(s)
Endotelina-1/análogos & derivados , Péptidos/química , Conformación Proteica , Receptores de Endotelina/agonistas , Secuencia de Aminoácidos , Endotelina-1/química , Cómputos Matemáticos , Datos de Secuencia Molecular , Receptor de Endotelina B , Soluciones
7.
Food Chem ; 161: 79-86, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-24837924

RESUMEN

Antimicrobial properties of ethanol and water extracts from eight Asteraceae species were investigated against three Gram positive (Staphylococcus aureus, MRSA and Bacillus cereus) and two Gram negative (Escherichia coli and Salmonella typhimurium) bacterial strains. Ethanol extracts from Centaurea scabiosa, Arctium minus, Taraxacum officinale, Centaurea nigra and Cirsium palustre demonstrated antimicrobial activity against strains of S. aureus, MRSA and B. cereus (MIC=187.5-365µg/ml). Ethanol extracts also had higher antioxidant activities and phenolic content demonstrating a link between these compounds and the bioactivity of these extracts. Further investigation into the phenolic content of ethanol extracts using UPLC-MS/MS lead to the identification and quantification of numerous phenolic compounds in all species including; 18 from Cirsium arvense, 16 from Cirsium vulgare, 19 from C. palustre, 15 from C. nigra, 17 from C. scabiosa, 14 from Sonchus asper, 17 from A. minus and 11 from T. officinale.


Asunto(s)
Antiinfecciosos/uso terapéutico , Antioxidantes/uso terapéutico , Asteraceae/microbiología , Cromatografía Liquida/métodos , Pruebas de Sensibilidad Microbiana , Espectrometría de Masas en Tándem/métodos
8.
Phytochemistry ; 98: 197-203, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24359632

RESUMEN

The combination of hyphenated techniques, LC-SPE-NMR and LC-MS, to isolate and identify minor isomeric compounds from an ethyl acetate fraction of Taraxacum officinale root was employed in this study. Two distinct fractions of 4-hydroxyphenylacetic acid derivatives of inositol were isolated and characterised by spectroscopic methods. The (1)H NMR spectra and MS data revealed two groups of compounds, one of which were derivatives of the di-4-hydroxyphenylacetic acid derivative of the inositol compound tetrahydroxy-5-[2-(4-hydroxyphenyl)acetyl] oxycyclohexyl-2-(4-hydroxyphenyl) acetate, while the other group consisted of similar tri-substituted inositol derivatives. For both fractions the derivatives of inositols vary in the number of 4-hydroxyphenylacetic acid groups present and their position and geometry on the inositol ring. In total, three di-substituted and three tri-substituted 4-hydroxyphenylacetic acid inositol derivates were identified for the first time along with a further two previously reported di-substituted inositol derivatives.


Asunto(s)
Inositol/química , Fenilacetatos/aislamiento & purificación , Raíces de Plantas/química , Taraxacum/química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Fenilacetatos/química , Espectrometría de Masas en Tándem
9.
Food Chem ; 141(4): 4295-302, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-23993618

RESUMEN

Freeze-dried fenugreek (Trigonella foenum-graecum) seeds and bitter melon (Momordica charantia) fruit were extracted sequentially using non-polar to polar solvents, with further separation carried out on polar extracts by molecular weight cut off dialysis. The fenugreek ethyl acetate crude extract (FGE3) demonstrated the highest antioxidant activity, in terms of Trolox Equivalents (TE), for both the DPPH (35.338±0.908 mg TE/g) and FRAP (77.352±0.627 mg TE/g) assays. This extract also contained the highest phenolic content, in terms of Gallic Acid Equivalents (GAE) (106.316±0.377 mg GAE/g). Despite having considerably lower antioxidant activity than fenugreek, the highest antioxidant activities for bitter fruit were observed in the hexane (BME1) and methanol hydrophilic<3.5 kDa dialysed (BME4<3.5 kDa) extracts, while the highest phenolic content was found in the methanol hydrophilic>3.5 kDa (BME4>3.5 kDa) dialysed extract. UPLC-MS was used to quantify 18 phenolic compounds from fenugreek and 13 from bitter melon in active crude extracts. The flavonoids apigenin-7-O-glycoside (1955.55 ng/mg) and luteolin-7-O-glycoside (725.50 ng/mg) were the most abundant compounds in FGE3, while bitter melon extracts contained only small amounts of mainly phenolic acids. A further 5 fenugreek and 1 bitter melon compounds were identified in trace amounts from the same extracts, respectively.


Asunto(s)
Antioxidantes/química , Momordica charantia/química , Fenoles/química , Extractos Vegetales/química , Trigonella/química , Cromatografía Líquida de Alta Presión , Frutas/química , Espectrometría de Masas
10.
J Pept Sci ; 3(6): 415-28, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9467970

RESUMEN

To understand the structural requirements for the biological activity of endothelin peptides and to develop receptor selective endothelin analogues further, the solution structure of the bicyclic 21 amino acid residue vasoactive peptide, endothelin-1, has been determined in methanol-d3/water using high-resolution 1H-NMR spectroscopy. To our knowledge, this solvent system has not previously been used in NMR studies of endothelin and/or endothelin-like peptides. Two-dimensional DQFCOSY, TOCSY and NOESY spectra were acquired along with a series of one-dimensional spectra. A total of 219 distance constraints and 5 angle constraints were derived from the NMR data. These were incorporated into structure calculations using distance geometry (DIANA) followed by simulated annealing and molecular dynamics. The resulting structures are characterized by an alpha-helical conformation, Lys9-His16, and residues Ser5-Asp8 form a type I beta-turn. The N-terminal region, which was not extensively constrained by NMR data, showed no preferred conformation. The C-terminal tail showed less extensive conformational averaging but no descriptive conformation could be observed. The results obtained in this study are in good agreement with previous proposals.


Asunto(s)
Endotelina-1/química , Espectroscopía de Resonancia Magnética , Metanol/química , Modelos Moleculares , Agua/química , Secuencia de Aminoácidos , Animales , Simulación por Computador , Humanos , Datos de Secuencia Molecular , Conformación Proteica , Soluciones , Porcinos
11.
J Pept Res ; 53(3): 223-33, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10231710

RESUMEN

The solution structure of a biologically active modified linear endothelin-1 analogue, ET1-21[Cys(Acm)1,15, Aib3,11, Leu7], has been determined for the first time by two-dimensional nuclear magnetic resonance spectroscopy in a methanol-d3/water solvent mixture. Out of approximately one hundred linear peptide analogues tested by biological assay, this peptide, together with a dozen others, showed significant ETB selective agonist activity. Here we report the solution structure of an ETB selective agonist of a full-length, synthetic linear endothelin analogue. The calculated structures indicate that the peptide adopts an alpha-helical conformation between residues Ser5-His16, whilst both N- and C-termini show no preferred conformation. These results suggest that the disulphide bridges normally associated with endothelin and sarafotoxin peptides may not necessarily be important for either ETB receptor binding activity or the formation of a helical conformation in solution.


Asunto(s)
Endotelina-1/análogos & derivados , Endotelina-1/química , Fragmentos de Péptidos/química , Receptores de Endotelina/química , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Biosíntesis de Péptidos , Péptidos , Receptor de Endotelina B , Homología de Secuencia de Aminoácido
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