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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.

SUBMITTER: Santos G

PROVIDER: S-EPMC4852538 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Santos Gesivaldo G Giraldez-Alvarez Lisandro Diego LD Ávila-Rodriguez Marco M Capani Francisco F Galembeck Eduardo E Neto Aristóteles Gôes AG Barreto George E GE Andrade Bruno B

Frontiers in aging neuroscience 20160502

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 th ...[more]

PMID: 27199743

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Project description:Background:Fumaria officinalis (F. officinalis, FO) has been used in many inflammatory and painful-ailments. The main aim of this work is to perform an in-depth bio-guided phytochemical investigation of F. officinalis by identifying its main-active ingredients. Optimizing pharmacokinetics via niosomal-preparation will also be done to enhance their in vivo antineuropathic and anti-inflammatory potentials, and to explore their possible-mechanism of actions. Methods:Bio-guided phytochemical-investigations including fractionation, isolation, chromatographic-standardization, and identification of the most active compound(s) were done. Optimized niosomal formulations of F. officinalis most active compound(s) were prepared and characterized. An in vivo biological-evaluation was done exploring acute, subchronic, and chronic alloxan-induced diabetes and diabetic-neuropathy, and carrageenan-induced acute inflammatory-pain and chronic-inflammatory edema. Results:In-vivo bio-guided fractionation and chromatographic phytochemical-analysis showed that the alkaloid-rich fraction (ARF) is the most-active fraction. ARF contained two major alkaloids; Stylopine 48.3%, and Sanguinarine 51.6%. In-vitro optimization, analytical, and in vivo biological-investigations showed that the optimized-niosome, Nio-2, was the most optimized niosomal formulation. Nio-2 had particle size 96.56?±?1.87 nm and worked by improving the pharmacokinetic-properties of ARF developing adequate entrapment-efficiency, rapid-degradation, and acceptable stability in simulated GI conditions. FO, ARF, and Nio 2 were the most potent antidiabetic and anti-inflammatory compounds. The reduction of the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and Interleukin 6 (IL-6), and elevation the anti-inflammatory factor IL-10 levels and amelioration of the in vivo oxidative-stress might be the main-mechanism responsible for their antinociceptive and anti-inflammatory activities. Conclusions:Fumaria officinalis most-active fraction was identified as ARF. This study offers an efficient and novel practical oral formulation ameliorating various inflammatory conditions and diabetic complications especially neuropathic-pain.

Dataset Information

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

Publications

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

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