scholarly journals Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dmitri Leonoudakis ◽  
Anand Rane ◽  
Suzanne Angeli ◽  
Gordon J. Lithgow ◽  
Julie K. Andersen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Glial Cells ◽  
Glial Activation ◽  
Inos Mrna ◽  
Potential Candidate ◽  
Bv2 Cells ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects in glial cells. Our results demonstrate that securinine significantly and dose-dependently suppressed the nitric oxide production in microglia and astrocytic cultures. In addition, securinine inhibited the activation of the inflammatory mediator NF-κB, as well as mitogen-activated protein kinases in lipopolysaccharide- (LPS-) stimulated BV2 cells. Additionally, securinine also inhibited interferon-γ- (IFN-γ-) induced nitric oxide levels and iNOS mRNA expression. Furthermore, conditioned media (CM) from securinine pretreated BV2 cells significantly reduced mesencephalic dopaminergic neurotoxicity compared with CM from LPS stimulated microglia. These findings suggest that securinine may be a potential candidate for the treatment of neurodegenerative diseases related to neuroinflammation.

Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease

2015 ◽  
Vol 73 ◽  
pp. 377-387 ◽  
Author(s):  
Mariza Bortolanza ◽  
Roberta Cavalcanti-Kiwiatkoski ◽  
Fernando E. Padovan-Neto ◽  
Célia Aparecida da-Silva ◽  
Miso Mitkovski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nitric Oxide Synthase ◽  
Rat Model ◽  
Glial Activation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase

scholarly journals Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
José Christian Machado Ximenes ◽  
Kelly Rose Tavares Neves ◽  
Luzia Kalyne A. M. Leal ◽  
Marta Regina Santos do Carmo ◽  
Gerly Anne de Castro Brito ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Valproic Acid ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Wide Spectrum ◽  
Temporal Cortex ◽  
Field Tests ◽  
Tnf Alpha ◽  
Potential Candidate ◽  
Anti Inflammatory

Parkinson’s disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson’s disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were observed not only in the CA1 and CA3 subfields of the hippocampus, but also in the temporal cortex. In conclusion, we showed that VA partly reversed the behavioral, neurochemical, histological, and immunohistochemical alterations observed in the untreated 6-OHDA-lesioned animals. These effects are probably related to the drug anti-inflammatory activity and strongly suggest that VA is a potential candidate to be included in translational studies for the treatment of neurodegenerative diseases as PD.

An Update on the Role of Nitric Oxide in the Neurodegenerative Processes of Parkinson's Disease

2016 ◽  
Vol 23 (24) ◽  
pp. 2666-2679 ◽  
Author(s):  
Félix Jiménez-Jiménez ◽  
Hortensia Alonso-Navarro ◽  
María Herrero ◽  
Elena García-Martín ◽  
José Agúndez
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease

scholarly journals Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson’s disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Musa Ozturk ◽  
Ashwin Viswanathan ◽  
Sameer A. Sheth ◽  
Nuri F. Ince
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pharmacological Treatment ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
High Frequency Oscillations ◽  
Stimulation Pulse ◽  
Main Challenge ◽  
Frequency Stimulation ◽  
Underlying Mechanisms

AbstractDespite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130–180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

scholarly journals High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Salman Sohrabi ◽  
Danielle E. Mor ◽  
Rachel Kaletsky ◽  
William Keyes ◽  
Coleen T. Murphy
Keyword(s):  
Neural Network ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Potential Candidate ◽  
Automated Scoring ◽  
C Elegans ◽  
Drug Candidates ◽  
Branched Chain ◽  
Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

Levodopa-induced dyskinesias in Parkinson’s disease increase cerebrospinal fluid nitric oxide metabolites’ levels

2021 ◽  
Author(s):  
Bruno L. Santos-Lobato ◽  
Mariza Bortolanza ◽  
Lucas César Pinheiro ◽  
Marcelo E. Batalhão ◽  
Ângela V. Pimentel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Nitric Oxide Metabolites

Anti-inflammatory assessment of 3-Acetylmyricadiol in LPS-Stimulated Raw 264.7 Macrophages

2021 ◽  
Vol 24 ◽  
Author(s):  
Gazanfar Ahmad ◽  
Reyaz Hassan ◽  
Neerupma Dhiman ◽  
Asif Ali
Keyword(s):  
Nitric Oxide ◽  
Cell Viability ◽  
Ethyl Acetate ◽  
Mtt Assay ◽  
Bark Extract ◽  
Maximum Effect ◽  
Potential Candidate ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

Background: Pentacyclic triterpenoids are a biologically active class of phytoconstituents with diverse pharmacological activity including anti-inflammatory action. Objective: In the current study, we isolated 3-Acetylmyricadiol, a pentacyclic triterpenoid, from the ethyl acetate bark-extract of Myrica esculenta and evaluated it for anti-inflammatory potential. Methods: The ethyl acetate bark-extract of the M. esculenta was subjected to column chromatography to isolate 3-Acetylmyricadiol. MTT assay was performed to check cell viability. The production of proinflammatory mediators like Nitric oxide, IL-6, TNF-α was observed after administration of 5, 10, 20 μM of 3-Acetylmyricadiol in LPS-activated Raw 246.7 macrophages by the reported methods. Results: MTT assay indicated more than 90% cell viability up to 20 μM of 3-Acetylmyricadiol. The administration of 3-Acetylmyricadiol inhibited the production of Nitric oxide, IL-6, TNF-α in a dose-dependent manner significantly in comparison to LPS treated cells. The maximum effect was observed at 20 μM of 3-Acetylmyricadiol which resulted in 52.37, 63.10, 55.37 % inhibition of Nitric oxide, IL-6, TNF-α respectively. Conclusion: Our study demonstrated the anti-inflammatory action of 3-Acetylmyricadiol and can serve as a potential candidate in the development of the clinically efficient anti-inflammatory molecule.

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