Search results for: MPTP
4 Neuroprotective Effects of Rosmarinic Acid in the MPTP Mouse Model of Parkinson's Disease
Authors: Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie
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Rosmarinic acid (RA) is a natural acid that is found in a variety of herbs, such as rosemary and has multiple biological activities such as antioxidative, anti-inflammatory and antiviral activities. In this study, we investigated the neuroprotective effects of RA on dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of Parkinson’s disease (PD). The mice received oral administration of RA before MPTP injection. Results showed that the tyrosine hydroxylase expression in SN reduced and the levels of dopamine and its metabolites in the striatum decreased in MPTP intoxicated PD mice. Pretreatment with RA significantly inhibited these changes. Further studies demonstrated that MPTP treatment increased the iron content, which was counteracted by pre-treatment with RA. In addition, RA could restore the decrease of superoxide dismutase (SOD) induced by MPTP. This study provides evidence that RA could suppress MPTP-induced degeneration of the nigrostriatal dopaminergic system by regulating iron content and the expression of SOD. Thus, RA might be clinically evaluated for the prevention of neurodegenerative diseases.Keywords: rosmarinic acid, Parkinson's disease, MPTP, dopaminergic system
Procedia PDF Downloads 2023 Pomegranate Attenuated Levodopa-Induced Dyskinesia and Dopaminergic Degeneration in MPTP Mice Models of Parkinson’s Disease
Authors: Mahsa Hadipour Jahromy, Sara Rezaii
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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate
Procedia PDF Downloads 4922 Involvement of Nrf2 in Kolaviron-Mediated Attenuation of Behavioural Incompetence and Neurodegeneration in a Murine Model of Parkinson's Disease
Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi
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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration
Procedia PDF Downloads 991 Synthesis of Pyrimidine-Based Polymers Consist of 2-{3-[4,6-Bis-(4-Hexyl-Thiophen-2-yl)-Pyrimidin-2-yl]Phenyl}-Thiazolo[5,4-B]Pyridine as Electron-Deficient Unit for Photovoltaics
Authors: Hyehyeon Lee, Juwon Yu, Juwon Kim, Raquel Kristina Leoni Tumiar, Taewon Kim, Juae Kim, Hongsuk Suh
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Recently, the development of photovoltaics is rapidly accelerating as one of green energy sources. So we designed pyrimidine-based polymers with 2-{3-[4,6-bis-(4-hexyl-thiophen-2-yl)-pyrimidin-2-yl]-phenyl}-thiazolo[5,4-b]pyridine (mPTP), as active layer substances for polymer solar cells. Polymers with push-pull types, mPTPBDT-12, mPTPBDT-EH, mPTPBDTT-EH and mPTPTTI, are comprised of electron pushing unit using benzo[1,2-b;3,4-b’]dithiophene (BDT) or 4,8-bis(5-thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (BDTT) or 6-(2-thienyl)-4H-thieno[3,2-b]indole(TTI) and electron pulling unit using mPTP. The device including mPTPTTI-12 indicated a VOC of 0.67 V, a JSC of 2.16 mA/cm², and a fill factor (FF) of 0.30, giving a power conversion efficiency (PCE) of 0.43%. The device including mPTPBDT-EH indicated a VOC of 0.56 V, a JSC of 2.64 mA/cm², and an FF of 0.30, giving a PCE of 0.44%. The device including mPTPBDTT-EH indicated a VOC of 0.44 V, a JSC of 2.45 mA/cm², and an FF of 0.29, giving a PCE of 0.31%. The device including mPTPTTI indicated a VOC of 0.72 V, a JSC of 4.95 mA/cm², and an FF of 0.32, giving a PCE of 1.15%. Therefore, mPTPBDT-12, mPTPBDT-EH, mPTPBDTT-EH and mPTPTTI were fabricated by Stille polymerization. Their optical properties were measured and the results show that pyrimidine-based polymers have a great promise to act as donor of active layer.Keywords: polymer solar cells, photovoltaics, thiazolopyridine, conjugated polymer
Procedia PDF Downloads 273