scholarly journals Artemisinin Attenuated Oxidative Stress and Apoptosis by Inhibiting Autophagy in MPP+-treated SH-SY5Y Cell 

2020 ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Artemisia Annua ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Neuroprotective Effects ◽  
Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40μM. The 20μM ART for 24h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20μM ART for 4h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP+ increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

scholarly journals Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cell

2020 ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Artemisia Annua ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Neuroprotective Effects ◽  
Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40 µM. The 20 µM ART for 24 h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20 µM ART for 4 h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP + increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

scholarly journals Blood Exosomes Have Neuroprotective Effects in a Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Sun ◽  
Zhe-Xu Ding ◽  
Xin Luo ◽  
Qing-Shan Liu ◽  
Yong Cheng
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amino Acid ◽  
Dopaminergic Neurons ◽  
Motor Coordination ◽  
Oxidized Lipids ◽  
Metabolomic Analysis ◽  
Neuroprotective Effects ◽  
And Control

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

scholarly journals α-Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone-Induced Rat Model of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1421 ◽  
Author(s):  
Hayate Javed ◽  
M. F. Nagoor Meeran ◽  
Sheikh Azimullah ◽  
Lujain Bader Eddin ◽  
Vivek Dhar Dwivedi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Proinflammatory Cytokines ◽  
Rat Model ◽  
Inflammatory Mediators ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effects ◽  
Dopaminergic Neurodegeneration

Rotenone (ROT), a plant-derived pesticide is a well-known environmental neurotoxin associated with causation of Parkinson’s disease (PD). ROT impairs mitochondrial dysfunction being mitochondrial complex-I (MC-1) inhibitor and perturbs antioxidant-oxidant balance that contributes to the onset and development of neuroinflammation and neurodegeneration in PD. Due to the scarcity of agents to prevent the disease or to cure or halt the progression of symptoms of PD, the focus is on exploring agents from naturally occurring dietary phytochemicals. Among numerous phytochemicals, α-Bisabolol (BSB), natural monocyclic sesquiterpene alcohol found in many ornamental flowers and edible plants garnered attention due to its potent pharmacological properties and therapeutic potential. Therefore, the present study investigated the neuroprotective effects of BSB in a rat model of ROT-induced dopaminergic neurodegeneration, a pathogenic feature of PD and underlying mechanism targeting oxidative stress, inflammation and apoptosis. BSB treatment significantly prevented ROT-induced loss of dopaminergic neurons and fibers in the substantia nigra and striatum respectively. BSB treatment also attenuated ROT-induced oxidative stress evidenced by inhibition of MDA formation and GSH depletion as well as improvement in antioxidant enzymes, SOD and catalase. BSB treatment also attenuated ROT-induced activation of the glial cells as well as the induction and release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and inflammatory mediators (iNOS and COX-2) in the striatum. In addition to countering oxidative stress and inflammation, BSB also attenuated apoptosis of dopaminergic neurons by attenuating downregulation of anti-apoptotic protein Bcl-2 and upregulation of pro-apoptotic proteins Bax, cleaved caspases-3 and 9. Further, BSB was observed to attenuate mitochondrial dysfunction by inhibiting mitochondrial lipid peroxidation, cytochrome-C release and reinstates the levels/activity of ATP and MC-I. The findings of the study demonstrate that BSB treatment salvaged dopaminergic neurons, attenuated microglia and astrocyte activation, induction of inflammatory mediators, proinflammatory cytokines and reduced the expression of pro-apoptotic markers. The in vitro study on ABTS radical revealed the antioxidant potential of BSB. The results of the present study are clearly suggestive of the neuroprotective effects of BSB through antioxidant, anti-inflammatory and anti-apoptotic properties in ROT-induced model of PD.

scholarly journals Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson’s Disease is Mediated by α7-Nicotinic Receptors

2020 ◽  
Vol 21 (19) ◽  
pp. 7329
Author(s):  
Eslam El Nebrisi ◽  
Hayate Javed ◽  
Shreesh K Ojha ◽  
Murat Oz ◽  
Safa Shehab
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Motor Behavior ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Intraperitoneal Administration ◽  
Neuroprotective Effects ◽  
Α7 Nachr

Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism.

scholarly journals Oxidative Stress, Mitochondrial Dysfunction, and Neuroprotection of Polyphenols with Respect to Resveratrol in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 918
Author(s):  
Heng-Chung Kung ◽  
Kai-Jung Lin ◽  
Chia-Te Kung ◽  
Tsu-Kung Lin
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Critical Role ◽  
Neuronal Loss ◽  
Ros Generation ◽  
Neuroprotective Effects ◽  
Dopaminergic Neuronal Loss

Parkinson’s disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss. The exact pathogenesis of PD is complex and not yet completely understood, but research has established the critical role mitochondrial dysfunction plays in the development of PD. As the main producer of cytosolic reactive oxygen species (ROS), mitochondria are particularly susceptible to oxidative stress once an imbalance between ROS generation and the organelle’s antioxidative system occurs. An overabundance of ROS in the mitochondria can lead to mitochondrial dysfunction and further vicious cycles. Once enough damage accumulates, the cell may undergo mitochondria-dependent apoptosis or necrosis, resulting in the neuronal loss of PD. Polyphenols are a group of natural compounds that have been shown to offer protection against various diseases, including PD. Among these, the plant-derived polyphenol, resveratrol, exhibits neuroprotective effects through its antioxidative capabilities and provides mitochondria protection. Resveratrol also modulates crucial genes involved in antioxidative enzymes regulation, mitochondrial dynamics, and cellular survival. Additionally, resveratrol offers neuroprotective effects by upregulating mitophagy through multiple pathways, including SIRT-1 and AMPK/ERK pathways. This compound may provide potential neuroprotective effects, and more clinical research is needed to establish the efficacy of resveratrol in clinical settings.

scholarly journals Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Leilei Chen ◽  
Yujv Huang ◽  
Xing Yu ◽  
Jiahong Lu ◽  
Wenting Jia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Dopaminergic Neurons ◽  
Cell Model ◽  
Neuronal Loss ◽  
Motor Dysfunction ◽  
Neuroprotective Effects ◽  
Drug Candidates ◽  
Low Dosage

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson’s disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

Neuroprotective Effect of Coptis chinensis in MPP+ and MPTP-Induced Parkinson’s Disease Models

2016 ◽  
Vol 44 (05) ◽  
pp. 907-925 ◽  
Author(s):  
Thomas Friedemann ◽  
Yue Ying ◽  
Weigang Wang ◽  
Edgar R. Kramer ◽  
Udo Schumacher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Coptis Chinensis

The rhizome of Coptis chinensis is commonly used in traditional Chinese medicine alone or in combination with other herbs to treat diseases characterized by causing oxidative stress including inflammatory diseases, diabetes mellitus and neurodegenerative diseases. In particular, there is emerging evidence that Coptis chinensis is effective in the treatment of neurodegenerative diseases associated with oxidative stress. Hence, the aim of this study was to investigate the neuroprotective effect of Coptis chinensis in vitro and in vivo using MPP[Formula: see text] and MPTP models of Parkinson’s disease. MPP[Formula: see text] treated human SH-SY5Y neuroblastoma cells were used as a cell model of Parkinson’s disease. A 24[Formula: see text]h pre-treatment of the cells with the watery extract of Coptis chinensis significantly increased cell viability, as well as the intracellular ATP concentration and attenuated apoptosis compared to the MPP[Formula: see text] control. Further experiments with the main alkaloids of Coptidis chinensis, berberine, coptisine, jaterorrhizine and palmatine revealed that berberine and coptisine were the main active compounds responsible for the observed neuroprotective effect. However, the full extract of Coptis chinensis was more effective than the tested single alkaloids. In the MPTP-induced animal model of Parkinson’s disease, Coptis chinensis dose-dependently improved motor functions and increased tyrosine hydroxylase-positive neurons in the substantia nigra compared to the MPTP control. Based on the results of this work, Coptis chinensis and its main alkaloids could be considered potential candidates for the development of new treatment options for Parkinson’s disease.

scholarly journals Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Renrong Wei ◽  
Cuiping Rong ◽  
Qingfeng Xie ◽  
Shouhai Wu ◽  
Yuchao Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Binding ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effect ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Cox 2

Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.

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