Evaluation of Newly Synthesized Chalcone Derivatives Effect on PC12 Cells in in Vitro Model of The Parkinson's Disease As a Potential Treatment

Abstract Chalcone is a common simple scaffold found in many naturally occurring compounds. Many Chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities, such as antioxidant, anti-inflammatory, induction of apoptosis, and angiogenesis. As the second most common neurodegenerative disease after Alzheimer's disease, Parkinson’s disease is most common motor function disorder. Even though this disease is not fully understood, processes such as oxidative stress and neuronal apoptosis are largely involved in its progress. As such, antioxidants are significant agents in slowing down the process through running interference in ROS production and apoptosis. Here, we present the effect of three newly synthesized Chalcone compounds on 6-OHDA-induced cytotoxicity on the PC12 cells in Parkinson's disease model by integrating several experimental (MTT assay, ROS assay, Annexin & PI assay, Western blotting P53, Bax, Bcl2) data and validating the results based on the interactional contribution equations of these compounds obtained from previous experimental and theoretical study carried out on the molecular resonance and interactional behavior of these compounds via Linear solvation energy relationship (LSER) model and time-dependent density functional theory and conﬁguration interaction calculations. We conclude that all three Chalcones have neuroprotective activity, and presented a reduction in ROS production and an increment in cell viability in the groups treated with 6-OHDA. This effect was observed at lower concentrations for all Chalcone compounds. At higher concentrations Chalcones 1 and 2 showed cytotoxicity. However, Chalcone 3 did not show any cytotoxicity, even for high doses, which points out the therapeutic potential of this Chalcone in reducing the dopaminergic cell destruction.

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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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The Ameliorative Effects of the Ethyl Acetate Extract ofSalicornia europaeaL. and Its Bioactive Candidate, Irilin B, on LPS-Induced Microglial Inflammation and MPTP-Intoxicated PD-Like Mouse Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6764756 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Joonsoo Kim ◽

Govindarajan Karthivashan ◽

Mee-Hyang Kweon ◽

Deuk-Hoi Kim ◽

Dong-Kug Choi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Therapeutic Potential ◽

Motor Deficits ◽

Resonance Spectroscopy ◽

Potential Candidate ◽

Nigrostriatal Pathway ◽

Salicornia Europaea ◽

Isolation And Purification

Hyperactivation of microglia, the resident innate immune cells of the central nervous system, exacerbates various neurodegenerative disorders, including Parkinson’s disease (PD). Parkinson’s disease is generally characterized by a severe loss of dopaminergic neurons in the nigrostriatal pathway, with substantial neuroinflammation and motor deficits. This was experimentally replicated in animal models, using neurotoxins, i.e., LPS (lipopolysaccharides) and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).Salicornia europaeaL. (SE) has been used as a dietary supplement in Korea and Europe for several years, due to its nutritional and therapeutic value. In this study, we intend to investigate the antineuroinflammatory and anti-PD-like effects of the bioactive fraction/candidate of the SE extract. Initially, we screened various fractions of SE extract using anin vitroantioxidant assay. The optimal fraction was investigated for itsin vitroantineuroinflammatory potential in LPS-stimulated BV-2 microglial cells andin vivoanti-PD-like potential in MPTP-intoxicated mice. Subsequently, to identify the potential candidate responsible for the elite therapeutic potential of the optimal fraction, we conducted antioxidant activity-guided isolation and purification; the bioactive candidate was structurally characterized using nuclear magnetic resonance spectroscopy and chromatographic techniques and further investigated for itsin vitroantioxidative and antineuroinflammatory potential. The results of our study indicate that SE-EA and its bioactive candidate, Irilin B, effectively alleviate the deleterious effect of microglia-mediated neuroinflammation and promote antioxidative effects. Thus, they exhibit potential as therapeutic candidates against neuroinflammatory and oxidative stress-mediated PD-like neurodegenerative complications.

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Comparison of the Protective Effects of Bee Venom Extracts with Varying PLA2 Compositions in a Mouse Model of Parkinson’s Disease

Toxins ◽

10.3390/toxins11060358 ◽

2019 ◽

Vol 11 (6) ◽

pp. 358 ◽

Cited By ~ 5

Author(s):

Kyung Hwa Kim ◽

Minhwan Kim ◽

Jaehwan Lee ◽

Hat Nim Jeon ◽

Se Hyun Kim ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Therapeutic Potential ◽

Bee Venom ◽

Neuroprotective Activity ◽

Protective Effects ◽

Active Components ◽

Therapeutic Benefits ◽

Pharmacologically Active

Bee venom contains a number of pharmacologically active components, including enzymes and polypeptides such as phospholipase A2 (PLA2) and melittin, which have been shown to exhibit therapeutic benefits, mainly via attenuation of inflammation, neurotoxicity, and nociception. The individual components of bee venom may manifest distinct biological actions and therapeutic potential. In this study, the potential mechanisms of action of PLA2 and melittin, among different compounds purified from honey bee venom, were evaluated against Parkinson’s disease (PD). Notably, bee venom PLA2 (bvPLA2), but not melittin, exhibited neuroprotective activity against PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP-induced behavioral deficits were also abolished after bvPLA2 treatment, depending on the PLA2 content. Further, bvPLA2 administration activated regulatory T cells (Tregs) while inhibiting inflammatory T helper (Th) 1 and Th17 cells in the MPTP mouse model of PD. These results indicate that bvPLA2, but not melittin, protected against MPTP and alleviated inflammation in PD. Thus, bvPLA2 is a promising and effective therapeutic agent in Parkinson’s disease.

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Crocetin Alleviates Inflammation in MPTP-Induced Parkinson’s Disease Models through Improving Mitochondrial Functions

Parkinson s Disease ◽

10.1155/2020/9864370 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Na Dong ◽

Zhong Dong ◽

Ying Chen ◽

Xiaosu Gu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mitochondrial Permeability Transition ◽

Therapeutic Potential ◽

Adenine Nucleotide ◽

Motor Deficits ◽

Dependent Manner ◽

Cyclophilin D ◽

Mitochondrial Functions

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Crocetin, derived from saffron, exerts multiple pharmacological properties, such as anti-inflammatory, antioxidant, antifatigue, and anticancer effects. However, the effect of crocetin on PD remains unclear. In this study, we designed experiments to investigate the effect of crocetin against MPTP-induced PD models and the underlying mechanisms. Our results showed that crocetin treatment attenuates MPTP-induced motor deficits and protects dopaminergic neurons. Both in vivo and in vitro experiments demonstrated that crocetin treatment decreased the expression of inflammatory associated genes and inflammatory cytokines. Furthermore, crocetin treatment protected mitochondrial functions against MPP+ induced damage by regulating the mPTP (mitochondrial permeability transition pore) viability in the interaction of ANT (adenine nucleotide translocase) and Cyp D (Cyclophilin D) dependent manner. Therefore, our results demonstrate that crocetin has therapeutic potential in Parkinson’s disease.

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Targeting Histone Deacetylases: A Novel Approach in Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2015/303294 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Sorabh Sharma ◽

Rajeev Taliyan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcriptional Activation ◽

Histone Deacetylases ◽

Therapeutic Potential ◽

Hdac Inhibitors ◽

Clinical Manifestations ◽

Future Research

The worldwide prevalence of movement disorders is increasing day by day. Parkinson’s disease (PD) is the most common movement disorder. In general, the clinical manifestations of PD result from dysfunction of the basal ganglia. Although the exact underlying mechanisms leading to neural cell death in this disease remains unknown, the genetic causes are often established. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the neurological disease conditions. The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the recent past, studies with HDAC inhibitors result in beneficial effects in bothin vivoandin vitromodels of PD. Various clinical trials have also been initiated to investigate the possible therapeutic potential of HDAC inhibitors in patients suffering from PD. The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. In this review, the authors have discussed the putative role of HDAC inhibitors in PD and associated abnormalities and suggest new directions for future research in PD.

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Interactive Responses of Enkephalin, δ-opioid Receptor and Dopamine Receptor D1/D2 to Hypoxia and/or MPP+ Stress in PC12 Cells

10.21203/rs.3.rs-1167672/v1 ◽

2021 ◽

Author(s):

Tao Chen ◽

Qing-Yu Wang ◽

Dong-Man Chao ◽

Yi-Dong Deng ◽

Yan-Hui Liu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopamine Receptor ◽

Pc12 Cells ◽

Opioid Receptor ◽

Mrna Level ◽

Cell Protection ◽

Endogenous Opioid ◽

Δ Opioid Receptor

Abstract Hypoxic/ischemic brain injury is a potential etiology of Parkinson’s disease (PD). There is evidence suggesting that the up-regulation of enkephalin, an endogenous opioid, in the midbrain may have a compensatory effect against Parkinson’s disease (PD) related motor symptoms. To explore the potential mechanism underlying this action, we investigated the effects of hypoxia and MPP+, a pathological inducer PD, on enkephalin, δ-opioid receptor (DOR, an enkephalin receptor), and prohormone convertases 1 and 2 (PC1/PC2) on in- vitro PD model of PC12 cells. We found that (1) short-term hypoxia could inducing cell protection by up-regulating the level of enkephalin, accompanied by the synergistic up-regulation of δ-opioid receptor (DOR) ; (2) a longer period of hypoxia or MPP+ insult accelerated the proteolysis of proenkephalin by up-regulating PC1/PC2 which might produce more active enkephalin and thus activating DOR for cell protection; (3) The levels of enkephalin and DOR decreased significantly after a prolonged hypoxia or MPP+ insult; and (4) a certain degree of hypoxia improved cell viability and enhance the transcription of dopamine D1/D2 receptorby increasing their mRNA level. Our findings suggest that hypoxia may induce an interactive reaction of enkephalin, DOR and dopamine receptor D1/D2, which is potentially beneficial for cell surviving to severe/prolonged hypoxia and PD condition.

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Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

10.21203/rs.3.rs-29059/v3 ◽

2021 ◽

Author(s):

Xiao Yan Sheng ◽

Shui Yuan Yang ◽

Xiao Min Wen ◽

Xin Zhang ◽

Yong Feng Ye ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Motor Behavior ◽

Neuroprotective Effect ◽

Signal Pathway ◽

Dopamine Neurons ◽

Therapeutic Modality ◽

Neuroprotective Effects

Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

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Biologically Active Echinulin-Related Indolediketopiperazines from the Marine Sediment-Derived Fungus Aspergillus niveoglaucus

Molecules ◽

10.3390/molecules25010061 ◽

2019 ◽

Vol 25 (1) ◽

pp. 61 ◽

Cited By ~ 2

Author(s):

Olga F. Smetanina ◽

Anton N. Yurchenko ◽

Elena V. Girich (Ivanets) ◽

Phan Thi Hoai Trinh ◽

Alexander S. Antonov ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Model ◽

In Vitro Models ◽

Biologically Active ◽

Neuroprotective Activity ◽

Chiral Hplc ◽

Cytoprotective Activity ◽

First Time

Seven known echinulin-related indolediketopiperazine alkaloids (1–7) were isolated from the Vietnamese sediment-derived fungus Aspergillus niveoglaucus. Using chiral HPLC, the enantiomers of cryptoechinuline B (1) were isolated as individual compounds for the first time. (+)-Cryptoechinuline B (1a) exhibited neuroprotective activity in 6-OHDA-, paraquat-, and rotenone-induced in vitro models of Parkinson’s disease. (−)-Cryptoechinuline B (1b) and neoechinulin C (5) protected the neuronal cells against paraquat-induced damage in a Parkinson’s disease model. Neoechinulin B (4) exhibited cytoprotective activity in a rotenone-induced model, and neoechinulin (7) showed activity in the 6-OHDA-induced model.

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Protective Effects and Mechanisms of Procyanidins on Parkinson’s Disease In Vivo and In Vitro

Molecules ◽

10.3390/molecules26185558 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5558

Author(s):

Juan Chen ◽

Yixuan Chen ◽

Yangfan Zheng ◽

Jiawen Zhao ◽

Huilin Yu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Antioxidant Activities ◽

Antioxidant Response ◽

Related Factor ◽

Protective Effects ◽

Neuroprotective Effects

This research assessed the molecular mechanism of procyanidins (PCs) against neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenylpyridinium (MPP+) induced Parkinson’s disease (PD) models. In vitro, PC12 cells were incubated with PCs or deprenyl for 24 h, and then exposed to 1.5 mM MPP+ for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were incubated with deprenyl or PCs in 400 μM MPTP for 4 days. Compared with MPP+/MPTP alone, PCs significantly improved antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), and decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, PCs significantly increased nuclear Nrf2 accumulation in PC12 cells and raised the expression of NQO1, HO-1, GCLM, and GCLC in both PC12 cells and zebrafish compared to MPP+/MPTP alone. The current study shows that PCs have neuroprotective effects, activate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and alleviate oxidative damage in MPP+/MPTP-induced PD models.

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Therapeutic Potential of a Polymer-Encapsulated L-Dopa and Dopamine-Producing Cell Line in Rodent and Primate Models of Parkinson's Disease

Cell Transplantation ◽

10.1177/096368979800700211 ◽

1998 ◽

Vol 7 (2) ◽

pp. 165-174

Author(s):

Mark D. Lindner ◽

Dwaine F. Emerich

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Ethical Issues ◽

Therapeutic Potential ◽

Polymer Membranes ◽

Timely Review ◽

Therapeutic Molecules ◽

Behavioral Improvement

Encapsulation of cells within polymer membranes prior to transplantation provides a novel means of achieving continuous, site-specific delivery of therapeutic molecules to the CNS. The use of encapsulated dopamine-secreting cells that can be transplanted directly into the striatum has particular appeal for the treatment of Parkinson's disease. This article provides a brief and timely review of the progress that has been made over the past decade using encapsulated PC12 cells as a means of delivering dopamine and l-DOPA to the striatum in rodent and primate models of Parkinson's disease. The polymer membranes are well tolerated and biocompatible. Encapsulated PC12 cells survive in vivo for up to 6 mo, they release dopamine into the surrounding host striatum, and they clearly improve behavioral function in both dopamine-depleted rodents and primates. Although these results are promising, fundamental issues remain concerning the extent of dopamine diffusion from the polymer membranes and the number of devices needed for behavioral improvement, and the duration and consistency of cell viability and device output. Nevertheless, this technology appears to be a promising means of avoiding many of the practical, societal, and ethical issues that have been associated with other transplantation approaches.

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