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

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

Chinese Medicine ◽

10.1186/s13020-021-00429-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xiaoyan Sheng ◽

Shuiyuan Yang ◽

Xiaomin Wen ◽

Xin Zhang ◽

Yongfeng 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. Conclusions 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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Biodegradable nanoparticles loaded with levodopa and/or curcumin for treatment of Parkinson’s disease

European Journal of Public Health ◽

10.1093/eurpub/ckab120.070 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Marco André Cardoso ◽

Bassam Felipe Mogharbel ◽

Ana Carolina Irioda ◽

Priscila Elias Ferreira Stricker ◽

Robson Camilotti Slompo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Neurodegenerative Disorder ◽

Toxicity Testing ◽

In Vitro Toxicity ◽

Age Related ◽

Wide Range ◽

Low Cytotoxicity

Abstract Background Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the standard gold drug available for the treatment of PD. Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, antitumor properties. Copolymers composed of poly(ethylene oxide) (PEO) and biodegradable polyesters like poly(ε-caprolactone) (PCL) that can self-assemble into nanoparticles (NP). This study describes the development of NH2-PEO-PCL diblock copolymer positively charged and modified by the addition of glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA and curcumin that would be able to pass the blood-brain barrier. Methods The NH2-PEO-PCL nanoparticles suspensions were prepared using a nanoprecipitation and solvent displacement method and were coated with GSH. NP was submitted to various characterizations assays, and to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NP to observe cytotoxicity. Results NP has successfully loaded L-DOPA and curcumin was stable after freeze-drying, capable of advancing into in vitro toxicity testing. After being treated up to 72 hours of various concentrations of L-DOPA and curcumin loaded NP Vero and PC12 cells, the viability of the treated cells maintained a high percentage indicating that the NPs are biocompatible. Conclusions NP consisting of NH2-PEO-PCL have been characterized as potential formulations for brain delivery of L-DOPA and curcumin, and obtained results also indicate that the developed biodegradable nanomicelles were blood compatible, presented low cytotoxicity even in longer exposure times.

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

10.21203/rs.3.rs-354679/v1 ◽

2021 ◽

Author(s):

Mona Farhadi ◽

Zahra Sanadgol ◽

Seyed Behnamedin Jameie ◽

Elmira Kashani ◽

Nader Noroozi Pesyan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pc12 Cells ◽

Density Functional ◽

Therapeutic Potential ◽

Biological Activities ◽

Neuroprotective Activity ◽

Ros Production ◽

Chalcone Derivatives

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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