Effect of Hypericum perforatum extract on behavioural studies in experimentally induced neurodegenerative disease

Parkinson's disease (PD) is a common neurodegenerative movement disease affecting a large number of people worldwide. In animals, the intracranial or systemical application of the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) can result in severe injury to the nigrostriatal dopaminergic system. Hypericum perforatum is a plant generally used as an antidepressant that also has anti-inflammatory and antioxidant properties. Hypericum perforatum has been used to lessen the mild to moderate symptoms of depression. The present study was done to find the effect of Hypericum perforatum methanolic extract pretreatment and post-treatment on behavioral studies in MPTP induced Parkinson’s disease model. The behavioral assessments were performed with a forced swim test, pole test, tail suspension test, and catalepsy test. Hypericum perforatum extract ameliorated depressive-like behavior better in post-treatment as compared with pretreatment group in MPTP model of Parkinson's disease. It can be said that Hypericum perforatum methanolic extract might be a therapeutic agent for the treatment of PD, but further clinical studies are required.

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Efficacy of Hypericum perforatum extract on ultrastructural changes in brain and oxidative damage in Parkinson’s disease

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl4.4556 ◽

2020 ◽

Vol 11 (SPL4) ◽

pp. 2793-2798

Author(s):

Chandran Satheesh Kumar ◽

Srinivasagam Raja Sankar ◽

Kaliyaperumal Prabu

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Parkinson Disease ◽

Hypericum Perforatum ◽

Disease Model ◽

Post Treatment ◽

Ultrastructural Changes ◽

Pre Treatment ◽

The Brain

Parkinson’s disease (PD) is a serious chronic and progressive neurological disorder. Hypericum perforatum (H. perforatum) is a plant generally used as an antidepressant and therapy for many neurodegenerative disorders. The present study evaluates the action of Hypericum perforatum extract on MPTP induced oxidative stress and ultrastructural changes in the Parkinson disease model. For this research study, Parkinson disease in mice were induced using MPTP and Hypericum perforatum methanolic extract were given in the pre-treatment and post-treatment condition. After the treatment, the oxidative stress was measured using TBARS levels and the activities of GSH, GPx, CAT and SOD in brain tissues. The ultrastructural changes in brain mitochondria caused by MPTP toxicity was studied after Hypericum perforatum extract therapy using TEM images. The present study showed that HPE extract is able to balance the oxidative stress and antioxidants in the brain tissue of MPTP administered rats. The damaged nuclei in the brain recovered to the normal condition due to this extract therapy. Finally, to conclude, Hypericum perforatum extract post-treatment offers potential brain protection against MPTP-induced Parkinson’s disease than pre-treatment.

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Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model

BioMed Research International ◽

10.1155/2019/2382563 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 17

Author(s):

Bharti Gaba ◽

Tahira Khan ◽

Md Faheem Haider ◽

Tausif Alam ◽

Sanjula Baboota ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Refractive Index ◽

Vitamin E ◽

Zeta Potential ◽

Droplet Size ◽

Disease Model ◽

Intranasal Delivery ◽

Behavioral Studies ◽

Swimming Test

Purpose. The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD). Methods. The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity. Results. Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of − 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. Conclusion. Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.

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Faculty Opinions recommendation of Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727495722.793564376 ◽

2019 ◽

Author(s):

Oliver Brüstle

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Model ◽

Dopamine Neurons ◽

Human Astrocytes

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Faculty Opinions recommendation of Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.729804646.793537492 ◽

2017 ◽

Author(s):

Ole Isacson ◽

Teresia Osborn

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Disease Model ◽

Ips Cell

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Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

Scientific Reports ◽

10.1038/s41598-021-90094-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jui-Chih Chang ◽

Yi-Chun Chao ◽

Huei-Shin Chang ◽

Yu-Ling Wu ◽

Hui-Ju Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Disease Model ◽

Intranasal Delivery ◽

The Difference ◽

And Migration ◽

6 Hydroxydopamine ◽

Locomotor Behaviors ◽

Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

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Observation of magnetic susceptibility changes within the thalamus: a comparative study between healthy and Parkinson’s disease afflicted cynomolgus monkeys using 7 T MRI

Journal of Analytical Science & Technology ◽

10.1186/s40543-019-0199-8 ◽

2019 ◽

Vol 10 (1) ◽

Author(s):

Sangwoo Kim ◽

Youngjeon Lee ◽

Chang-Yeop Jeon ◽

Yeung Bae Jin ◽

Sukhoon Oh ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Parkinson’S Disease ◽

Positron Emission Tomography ◽

Parkinson's Disease ◽

Magnetic Resonance ◽

Disease Model ◽

Emission Tomography ◽

Resonance Imaging ◽

Cynomolgus Monkeys ◽

Positron Emission

Abstract Background Although the thalamus is known to modulate basal ganglia function related to motor control activity, the abnormal changes within the thalamus during distinct medical complications have been scarcely investigated. In order to explore the feasibility of assessing iron accumulation in the thalamus as an informative biomarker for Parkinson’s disease (PD), this study was designed to employ quantitative susceptibility mapping using a 7 T magnetic resonance imaging system in cynomolgus monkeys. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-injected cynomolgus monkey and a healthy control (HC) were examined by 7 T magnetic resonance imaging. Positron emission tomography with 18F-N-(3-fluoro propyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane was also employed to identify the relationship between iron deposits and dopamine depletion. All acquired values were averaged within the volume of interest of the nigrostriatal pathway. Findings Compared with the HC, the overall elevation of iron deposition within the thalamus in the Parkinson’s disease model (about 53.81% increase) was similar to that in the substantia nigra (54.81%) region. Substantial susceptibility changes were observed in the intralaminar part of the thalamus (about 70.78% increase). Additionally, we observed that in the Parkinson’s disease model, binding potential values obtained from positron emission tomography were considerably decreased in the thalamus (97.51%) and substantia nigra (92.48%). Conclusions The increased iron deposition in the thalamus showed negative correlation with dopaminergic activity in PD, supporting the idea that iron accumulation affects glutaminergic inputs and dopaminergic neurons. This investigation indicates that the remarkable susceptibility changes in the thalamus could be an initial major diagnostic biomarker for Parkinson’s disease-related motor symptoms.

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Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽

10.1177/17590914211009730 ◽

2021 ◽

Vol 13 ◽

pp. 175909142110097

Author(s):

Kui Cui ◽

Fan Yang ◽

Turan Tufan ◽

Muhammad U. Raza ◽

Yanqiang Zhan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcription Factors ◽

Disease Model ◽

Neuronal Loss ◽

Mrna Levels ◽

Gene Therapies ◽

Protein Levels ◽

Dopaminergic Systems ◽

And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

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Cytokinin Plant Hormones Have Neuroprotective Activity in In Vitro Models of Parkinson’s Disease

Molecules ◽

10.3390/molecules26020361 ◽

2021 ◽

Vol 26 (2) ◽

pp. 361

Author(s):

Gabriel Gonzalez ◽

Jiří Grúz ◽

Cosimo Walter D’Acunto ◽

Petr Kaňovský ◽

Miroslav Strnad

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Neuronal Cell Death ◽

Disease Model ◽

Neuronal Cell ◽

Zeatin Riboside ◽

Neuroprotective Activity ◽

Protective Activity

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson’s disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.

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