SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection.Fil: Santos, Gesivaldo. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Giraldez Alvarez, Lisandro Diego. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Ávila Rodriguez, Marco. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Galembeck, Eduardo. Universidade Estadual de Campinas; BrasilFil: Gôes Neto, Aristóteles. Universidade Estadual de Feira de Santana; BrasilFil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaFil: Andrade, Bruno. Universidade Estadual do Sudoeste da Bahia; Brasi

Application of computational quantum chemistry to chemical processes involved in mass spectrometry

The field of application of mass spectrometry (MS) has increased considerably due to the development of ionization techniques. Other factors that have stimulated the use of MS are the tandem mass spectrometry (MS/MS) and sequential mass spectrometry (MSn) techniques. However, the interpretation of the MS/MS and MSn data may lead to speculative conclusions. Thus, various quantum chemical methods have been applied for obtaining high quality thermochemical data in gas phase. In this review, we show some applications of computational quantum chemistry to understand the formation and fragmentation of gaseous ions of organic compounds in a MS analysis.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)FAPESPCNP

Sur1 Receptor Interaction With Hesperidin And Linarin Predicts Possible Mechanisms Of Action Of Valeriana Officinalis In Parkinson

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection. © 2016 Santos, Giraldez-Alvarez, ávila-Rodriguez, Capani, Galembeck, Neto, Barreto and Andrade.8MA

A Fragmentation study of di-acidic mycosporine-like amino acids in electrospray and nanospray mass spectrometry

Two mycosporine (MAAs), containing an extra acid function, were analyzed by nanospray and electrospray ionization tandem mass spectrometry. In contrast to the previous studies it is demonstrated that no significant characteristic methyl radical loss occurred in positive mode. The fragmentation pathway in negative mode was also proposed in this work, along with theoretical calculations to characterize the site of protonation.No presente estudo, duas micosporinas (MAAs) contendo um segundo ácido carboxílico foram submetidas à fragmentação em eletrospray e nanospray em diferentes equipamentos. Em contraste com resultados anteriores, a eliminação de radical metila no modo positivo de análise foi um processo minoritário de fragmentação. Neste trabalho apresentamos também a via de fragmentação destas substâncias em modo negativo e cálculos teóricos para caracterizar os sítios de protonação.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Fragmentation study of di-acidic mycosporine-like amino acids in electrospray and nanospray mass spectrometry

No presente estudo, duas micosporinas (MAAs) contendo um segundo ácido carboxílico foram submetidas à fragmentação em eletrospray e nanospray em diferentes equipamentos. Em contraste com resultados anteriores, a eliminação de radical metila no modo positivo de análise foi um processo minoritário de fragmentação. Neste trabalho apresentamos também a via de fragmentação destas substâncias em modo negativo e cálculos teóricos para caracterizar os sítios de protonação. Two mycosporine (MAAs), containing an extra acid function, were analyzed by nanospray and electrospray ionization tandem mass spectrometry. In contrast to the previous studies it is demonstrated that no significant characteristic methyl radical loss occurred in positive mode. The fragmentation pathway in negative mode was also proposed in this work, along with theoretical calculations to characterize the site of protonation. Keywords: mycosporine, nanoESI-MS/MS, ESI-MS/MS, natural products, algae Introduction Mycosporine-like amino acids (MAAs) are a group of chemically related, water soluble compounds responsible for UV photoprotection in a diverse range of organisms including invertebrates, fish, bacteria, cyanobacteria, micro-and macroalgae. 1-3 These compounds are chemically characterised by the presence of either a cyclohexenone or cyclohexenimine chromophore conjugated with a substituent nitrogen of an amino acid, amino alcohol or amino group 1 MAAs normally show a strong UV absorption between 310 and 360 nm with high molar extinction coefficients. These characteristics indicate a possible photoprotective role that has been demonstrated in a number of studies 11-13 17 In the last few years, nanospray ionisation (nanoESI) is beginning to increase in importance, especially with the development of automated systems using 'chips' (arrays of uniform nanospray needles that are used only once to avoid contamination). 21 NanoESI offers the possibility of improved sensitivity and lower sample consumption over conventional ESI for the analysis of natural products. 22 This is especially important for the study of extracts from biological and medicinal sources when often only a very small amount of material is available. In 'chip based' nanoESI, the analyte solution is sprayed from a conducting pipette tip pressed against the rear of a chip using a small gas pressure and much lower voltages to create the spray. Recently, analysis of some natural antioxidants (retinoids Experimental Chemicals All solvents used were HPLC grade (Tedia, J. Baker and Fisher). Water was purified using a Milli-Q system (Millipore, Bedford, MA, USA). Trifluoroacetic acid (99.9%) was purchased from Aldrich. Galena Química e Farmacêutica Ltda/Brazil kindly supplied the standards of shinorine and porphyra-334 (product Helioguard ® 365-Porphyra umbilicalis extracts) Instrumentation Nanospray ionisation analyses were performed on two quadrupole-time of flight hybrid instruments: (a) an UltrOTOF-Q (Bruker Daltonics, Billerica, MA) using Tip™ Emittek (glass tip capillaries working with 500 V) or (b) a QStar-XL (Applied Biosystems, Warrington, UK) using a Nanomate HD automatic 'chip based' nanospray system (Advion Biosciences, Norwich, UK). The Nanomate was set for 5 µL of solution to be aspirated and sprayed through a Nanomate 400 chip at 1.45 kV, with a nitrogen back pressure of 0.4 psi. On both instruments, the ion source gas and curtain gas were nitrogen. Electrospray ionisation analyses were performed on five instruments: (a) an Apex 4 7.0 Tesla Fouriertransform ion-cyclotron resonance mass spectrometer (Bruker Daltonics, Billerica, MA, USA). Samples were directly infused into the Apollo electrospray source from a syringe pump at 100 µL h -1 . Analyses were performed at a capillary voltage, of 4600V and capillary exit potential of 200 V (except were indicated otherwise). The N 2 drying gas temperature was 200 °C. A mixture of PEG grades was used as an external calibrant for accurate-mass ESI analysis; (b) on a quadrupole-time of flight instrument (UltrOTOF-Q, Bruker Daltonics, Billerica, MA). The analyses were performed in positive ion ESI mode at a capillary voltage of 3400 V and N 2 drying gas temperature of 180 °C. NaTFA 10 mmol L -1 was used as a standard for internal and external calibration; (c) on a QStar-XL quadrupole-time-of-flight instrument (Applied Biosystems, Warrington, UK); (d) on a Quattro-LC triple quadrupole mass spectrometer (Micromass, Manchester, UK); (e) on an Esquire HCT ion trap instrument (Bruker Daltonics, Billerica, MA, USA) using a syringe pump (Cole-Parmer, Vernon Hills, IL, USA). Ion trap analyses were performed using nitrogen as the nebulising and drying gas and helium as the bath gas (4×10 -6 mbar). Theoretical calculations All calculations were performed in Gaussian 03 27 suite of programs using the B3LYP/6-31+G(d,p) model. 28,29 The geometries of neutral and protonated species were optimised and the potential energy surface minima were indicated by analysis of vibrational frequencies. The gasphase basicity and proton affinity were calculated via a protonation reaction, using Gibbs energies and enthalpies, respectively. 30 Cardozo et al. 1627 Vol. 20, No. 9, 2009 Results and Discussion Mycosporine-like amino acids with one acidic function were previously analysed by positive mode ESI sequential mass spectrometry (at high-resolution and accurate-mass). The loss of a methyl radical by the homolytic cleavage of the O-C bond was observed to be the preferred fragmentation pathway. As expected, analysis in negative ion mode Conclusions These results indicate that the presence of a second carboxylic acid function significantly reduces the intensity of the observed product ions from the radical methyl cleavage in positive mode MS/MS. As expected, in the negative ion mode, the radical fragmentation pathway does not occur. Taken together, these results confirm the importance of careful selection of the product ions used for analytical protocols for the analysis of crude extracts containing MAAs where the presence of the second acid function may change the fragmentation behavior and the classical analysis of loss of methyl radical may lead to the wrong conclusions during screening for MAAs