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

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.

Download Full-text

Neuroprotective Effects of San-Huang-Xie-Xin-Tang in the MPP+/MPTP Models of Parkinson’s DiseaseIn VitroandIn Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/501032 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Yi-Ching Lo ◽

Yu-Tzu Shih ◽

Yu-Ting Tseng ◽

Hung-Te Hsu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Alternative Therapy ◽

Disease Model ◽

Substantia Nigra Pars Compacta ◽

Protective Effects ◽

Neuroprotective Effects ◽

Complementary And Alternative Therapy

San-Huang-Xie-Xin-Tang (SHXT), composed ofCoptidis rhizoma, Scutellariae radix, andRhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1–methyl–4–phenylpyridinium (MPP+)/1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) models of Parkinson’s disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP+in vitroand MPTPin vivo. In MPP+-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP+-inducedgp91phoxactivation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP+-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson’s disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection.

Download Full-text

Neuroprotective Effects and Mechanisms of Procyanidins In Vitro and In Vivo

Molecules ◽

10.3390/molecules26102963 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2963

Author(s):

Juan Chen ◽

Yixuan Chen ◽

Yangfan Zheng ◽

Jiawen Zhao ◽

Huilin Yu ◽

...

Keyword(s):

Antioxidant Activities ◽

Antioxidant Response ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Quinone Oxidoreductase ◽

Neuroprotective Effects ◽

Glutamate Cysteine Ligase ◽

Pheochromocytoma Cells

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 μg/mL) or N-Acetyl-L-cysteine (NAC) (20 μM) for 24 h, and then incubated with 200 μM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 μM) or PCs (4, 8 or 16 μg/mL) in the absence or presence of 300 μM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.

Download Full-text

Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5074367 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Pei-Cih Wei ◽

Guey-Jen Lee-Chen ◽

Chiung-Mei Chen ◽

Yih-Ru Wu ◽

Yi-Jing Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Indole Derivative ◽

Caspase 3 ◽

Related Factor ◽

Protective Effects ◽

Neuronal Viability ◽

Starting Point

Parkinson’s disease (PD) is a common neurodegenerative disease accompanied by a loss of dopaminergic (DAergic) neurons. The development of therapies to prevent disease progression is the main goal of drug discovery. There is increasing evidence that oxidative stress and antioxidants may contribute to the pathogenesis and treatment of PD, respectively. In the present study, we investigated the antioxidative protective effects of the indole-derivative compound NC001-8 in DAergic neurons derived from SH-SY5Y cells and PD-specific induced pluripotent stem cells (PD-iPSCs) carrying a PARKIN ex5del mutation. In SH-SY5Y-differentiated DAergic neurons under 1-methyl-4-phenylpyridinium (MPP+) treatment, NC001-8 remarkably reduced the levels of reactive oxygen species (ROS) and cleaved caspase 3; upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H dehydrogenase, quinone 1 (NQO1); and promoted neuronal viability. In contrast, NRF2 knockdown abolished the effect of NC001-8 on the reduction of ROS and improvement of neuronal viability. In H2O2-treated DAergic neurons differentiated from PD-iPSCs, NC001-8 rescued the aberrant increase in ROS and cleaved caspase 3 by upregulating NRF2 and NQO1. Our results demonstrated the protective effect of NC001-8 in DAergic neurons via promoting the NRF2 antioxidative pathway and reducing ROS levels. We anticipate that our present in vitro assays may be a starting point for more sophisticated in vivo models or clinical trials that evaluate the potential of NC001-8 as a disease modifier for PD.

Download Full-text

Protective effects of saffron and its constituent crocetin to motor symptoms, short life span and rough-eyed phenotypes in the fly models of Parkinson’s disease in vivo

10.1101/2020.12.06.408997 ◽

2020 ◽

Author(s):

Eiji Inoue ◽

Takahiro Suzuki ◽

Yasuharu Shimizu ◽

Keiichi Sudo ◽

Haruhisa Kawasaki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Life Span ◽

Neurodegenerative Disorder ◽

Neuronal Cell ◽

Crocus Sativus ◽

Motor Symptoms ◽

Protective Effects

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in A30P fly PD model in eye. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

Download Full-text

Protective effects of SUN N8075, a novel agent with antioxidant properties, in in vitro and in vivo models of Parkinson's disease

Brain Research ◽

10.1016/j.brainres.2008.02.073 ◽

2008 ◽

Vol 1214 ◽

pp. 169-176 ◽

Cited By ~ 17

Author(s):

A. Oyagi ◽

Y. Oida ◽

H. Hara ◽

H. Izuta ◽

M. Shimazawa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Antioxidant Properties ◽

Protective Effects ◽

In Vivo Models ◽

Novel Agent

Download Full-text

Camptothecin regulates microglia polarization and exerts neuroprotective effects via the AKT/Nrf2/HO-1-NF-κB signal axis in vivo and in vitro

10.21203/rs.3.rs-27607/v1 ◽

2020 ◽

Author(s):

dewei he ◽

dianfeng liu ◽

ang zhou ◽

xiyu gao ◽

yufei zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Cell Line ◽

Dopaminergic Neuron ◽

Inflammatory Responses ◽

Neuroprotective Effects ◽

Microglia Polarization

Abstract Background Parkinson's disease (PD), the second largest neurodegenerative disease seriously affects human health. Microglia, the main immune cells in the brain participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidences suggest that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson's disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. Therefore, we aim to explore the effect of CPT on microglia polarization and its underlying mechanism on neuroinflammation. Methods C57BL/6 mice (25–30 g) were injected LPS or PBS into the substantia nigra (SN). Open-Field Test and Immunohistochemistry were performed to test the dyskinesia of mice and the loss of neurons in the substantia nigra (SN). Microglia cell line BV-2, the neuroblastoma SH-SY5Y and dopaminergic neuron MN9D cell were cultured. Cytotoxicity assay, reverse transcription quantitative real-time polymerase chain reaction (RT-PCR), Western blot, ELISA and Immunofluorescence staining were performed. All results were presented with mean ± SD. Results In vivo, CPT improved dyskinesia of mice, reduced the loss of neurons in the substantia nigra (SN) and inhibited neuro-inflammatory responses in LPS-injected mice. In vitro, CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1-NF-κB signal axis. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from neurotoxicity of mediated by microglia activation. Conclusion CPT regulates the microglia polarization phenotype via the AKT/Nrf2/HO-1-NF-κB signal axis, inhibits neuro-inflammatory responses and exerts neuroprotective effects in vivo and in vitro.

Download Full-text

A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson’s Disease

Molecules ◽

10.3390/molecules26175371 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5371

Author(s):

Ying Guo ◽

Zhizhong Ma ◽

Xianling Ning ◽

Ying Chen ◽

Chao Tian ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Inflammatory Responses ◽

Neuroprotective Effect ◽

Detoxification Enzymes ◽

Mitogen Activated Protein Kinase ◽

Related Factor ◽

Apoptosis Pathway

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson’s disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.

Download Full-text

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

Download Full-text

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.

Download Full-text