title: SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.
abstract: 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.
authors.affiliation: Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia Jequié, Brazil.
authors.forename: Gesivaldo
authors.initials: G
authors.lastname: Santos
authors.affiliation: Programa Nacional de Pós-Doutorado (PNPD-CAPES), Departamento de Química e Exatas, Universidade Estadual do Sudoeste da Bahia Jequié, Brazil.
authors.forename: Lisandro Diego
authors.initials: LD
authors.lastname: Giraldez-Alvarez
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana Bogotá, DC, Colombia.
authors.forename: Marco
authors.initials: M
authors.lastname: Ávila-Rodriguez
authors.affiliation: Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET Buenos Aires, Argentina.
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas-UNICAMP Campinas, São Paulo, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Galembeck
authors.affiliation: Departamento de Ciências Biológicas, Universidade Estadual de Feira de Santana Feira de Santana, Brazil.
authors.forename: Aristóteles Gôes
authors.initials: AG
authors.lastname: Neto
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad JaverianaBogotá, DC, Colombia; Instituto de Ciencias Biomédicas, Universidad Autónoma de ChileSantiago, Chile; Universidad Científica del SurLima, Peru.
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
authors.affiliation: Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia Jequié, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Andrade
keywords: GABAA; Parkinson disease; SUR1; Valeriana officinalis; neuroprotection