Neuroprotective effects of Onion (Allium cepa) Ethanolic Extract on Animal Model of Parkinson's Disease Induced by   6-hydroxydopamine: A Behavioral, Biochemical, and Histological Study

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

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NEUROPROTECTIVE EFFECTS OF A SELECTIVEN-METHYL-d-ASPARTATE NR2B RECEPTOR ANTAGONIST IN THE 6-HYDROXYDOPAMINE RAT MODEL OF PARKINSON'S DISEASE

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.2008.05046.x ◽

2008 ◽

Vol 35 (11) ◽

pp. 1388-1394 ◽

Cited By ~ 13

Author(s):

KR Leaver ◽

HN Allbutt ◽

NJ Creber ◽

M Kassiou ◽

JM Henderson

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Receptor Antagonist ◽

Rat Model ◽

Neuroprotective Effects ◽

6 Hydroxydopamine ◽

Nr2b Receptor

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Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson’s disease

Neuroscience ◽

10.1016/j.neuroscience.2012.09.063 ◽

2012 ◽

Vol 227 ◽

pp. 305-312 ◽

Cited By ~ 71

Author(s):

T. Tuon ◽

S.S. Valvassori ◽

J. LOPES-BORGES ◽

T. Luciano ◽

C.B. Trom ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Model ◽

Physical Training ◽

Neuroprotective Effects

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KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease

Neurotherapeutics ◽

10.1007/s13311-021-01097-4 ◽

2021 ◽

Author(s):

Min-Ho Nam ◽

Jong-Hyun Park ◽

Hyo Jung Song ◽

Ji Won Choi ◽

Siwon Kim ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Therapeutic Potential ◽

Motor Dysfunction ◽

Monoamine Oxidase B ◽

Nigrostriatal Pathway ◽

Neuroprotective Effects ◽

Mao B ◽

6 Hydroxydopamine ◽

Mptp Model

AbstractMonoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.

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Hesperetin protects SH-SY5Y cells against 6- hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i6.12 ◽

2020 ◽

Vol 19 (6) ◽

pp. 1197-1201 ◽

Cited By ~ 1

Author(s):

Jing Li ◽

Yue Liu ◽

Li Wang ◽

Zhaowei Gu ◽

Zhigang Huan ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Viability ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Neuroprotective Effects ◽

Ldh Release ◽

6 Hydroxydopamine

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

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