scholarly journals Nanostructure Lipid Carriers Enhance Alpha-Mangostin Neuroprotective Efficacy In Mice With Rotenone-Induced Neurodegeneration

2021 ◽  
Author(s):  
Romkase Sakamula ◽  
Teerapong Yata ◽  
Wachiryah Thong-asa
Keyword(s):  
Superoxide Dismutase ◽  
Motor Cortex ◽  
Substantia Nigra ◽  
Neurodegenerative Disease ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Natural Antioxidants ◽  
Motor Deficits ◽  
Nissl Staining ◽  
Neuroprotective Effects

Abstract Neurodegenerative disease, for instance, Parkinson’s disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor deficits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD+αM, and PD+ αM-NLC groups. Vehicle, αM (25 mg/kg/48 h), and αM-NLC (25 mg/kg/48 h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5 mg/kg/48 h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone significantly induced motor deficits concurrent with significant SNc, striatum, and motor cortex neuronal reduction and significantly decreased TH intensity in SNc (p < 0.05). The significant reduction of brain superoxide dismutase activity (p < 0.05) was also detected. Administrations of αM and αM-NLC significantly reduced motor deficits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC significantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with significantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative stress. Moreover, αM-NLC exhibited broad protection against rotenone-induced neurodegeneration that was not limited to nigrostriatal structures and emphasized the benefit of NLC in enhancing αM neuroprotective effects.

scholarly journals Neuroprotective Effect of Nortriptyline in Overt Hepatic Encephalopathy Through Attenuation of Mitochondrial Dysfunction

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141881058 ◽  
Author(s):  
Ji Heun Jeong ◽  
Do Kyung Kim ◽  
Nam-Seob Lee ◽  
Young-Gil Jeong ◽  
Ho Won Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatic Encephalopathy ◽  
Substantia Nigra ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Apoptotic Pathway ◽  
Duct Ligation ◽  
Overt Hepatic Encephalopathy

Hyperammonemia associated with overt hepatic encephalopathy (OHE) causes excitotoxic neuronal death through activation of the cytochrome C (CytC)-mediated mitochondria-dependent apoptotic pathway. We tested the therapeutic effect of nortriptyline (NT), a mitochondrial permeability transition pore (mPTP) blocker that can possibly inhibit mitochondrial CytC efflux to the cytosol on in vivo and in vitro OHE models. After ensuring the generation of OHE rats, established by bile duct ligation (BDL), they were intraperitoneally administered either 20 mg/kg NT (i.e., BDL+NT) or another vehicle (i.e., BDL+VEH) for 14 days. Compared with the control, BDL+VEH showed an increment of motor deficits, cell death, synaptic loss, apoptosis, and mitochondria with aberrant morphology in substantia nigra compacta dopaminergic (DA-ergic) neurons. However, the extent was significantly reversed in BDL+NT. Subsequently, we studied the neuroprotective mechanism of NT using PC-12 cells, a DA-ergic cell line, which exposed glutamate used as an excitotoxin. Compared with the control, the cells exposed to 15 mM glutamate (i.e., GLU) showed incremental cell death, apoptosis, and demise in mitochondrial respiration. Importantly, efflux of CytC from mitochondria to cytosol and the dissipation of mitochondrial membrane potential (△Ψm), an indicator of mPTP opening, were prominent in GLU. However, compared with the GLU, the cells cotreated with 10 μM NT (i.e., GLU+NT) showed a significant reduction in the aforementioned phenomenon. Together, we concluded that NT can be used for OHE therapeutics, mitigating the excitotoxic death of substantia nigra compacta DA-ergic neurons via mPTP-associated mitochondrial dysfunction inhibition.

scholarly journals The Neuroprotective Effect of GPR4 Inhibition through Attenuation of Caspase Mediated Apoptotic Cell Death in MPTP Induced Mouse Model of Parkinson’s Disease

2021 ◽  
Author(s):  
Md. Ezazul Haque ◽  
Shofiul Azam ◽  
Mahbuba Akther ◽  
Duk-Yeon Cho ◽  
Kim In Su ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Apoptotic Cell Death ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Mice Model ◽  
Dopaminergic Neuronal Loss

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson&rsquo;s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

scholarly journals Benefits of Betanin in Rotenone-Induced Parkinson Mice

2021 ◽  
Author(s):  
Wachiryah Thong-asa ◽  
Sujira Jedsadavitayakol ◽  
Suchawalee Jutarattananon
Keyword(s):  
Superoxide Dismutase ◽  
Tyrosine Hydroxylase ◽  
Neuronal Degeneration ◽  
Reduced Glutathione ◽  
Neuroprotective Effect ◽  
Motor Dysfunction ◽  
Rotarod Test ◽  
Neuroprotective Effects ◽  
Disease Therapy ◽  
Antioxidative Property

Abstract The present study aimed to investigate betanin’s neuroprotective effect in mice with rotenone-induced Parkinson-like motor dysfunction and neurodegeneration. Forty male ICR mice were divided into 4 groups: Sham-veh, Rot-veh, Rot-Bet100 and Rot-Bet200. Rotenone (Rot) at 2.5 mg/kg/48 h was subcutaneous injected, and betanin (Bet) at 100 and 200 mg/kg/48 h were given alternately with the Rot injections in Rot-Bet groups for 6 weeks. Motor dysfunctions were evaluated weekly using hanging wire and rotarod tests. Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), neuronal degeneration in the motor cortex (MC), striatum (Str) and substantia nigra par compacta (SNc) were evaluated. The immunohistochemical densities of tyrosine hydroxylase (TH) in Str and in SNc were also measured. We found that rotenone significantly decreased the time to fall in a hanging wire test after the 4th week and after the rotarod test at the 6th week (p<0.05). The percentage of neuronal degeneration in MC, Str and SNc (p<0.05) significantly increased, and the TH density in Str and in SNc (p<0.05) significantly decreased. Betanin at 100 and 200 mg/kg significantly prevented MC, Str and SNc neuronal degeneration (p<0.05) and prevented the decrease of TH density in Str and in SNc (p<0.05). These findings appeared concurrently with improved effects on the time to fall in hanging wire and rotarod tests (p<0.05). Treatment with betanin significantly prevented increased MDA levels and boosted GSH, CAT and SOD activities (p<0.05). Betanin exhibits neuroprotective effects against rotenone-induced Parkinson in mice regarding both motor dysfunction and neurodegeneration. Betanin’s neurohealth benefit relates to its powerful antioxidative property. Therefore, betanin use in neurodegenerative disease therapy is interesting to study.

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chung-Che Lu ◽  
Tee-Tau Eric Nyam ◽  
Jinn-Rung Kuo ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glutamate Receptor ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Abstract Background The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). Methods Anesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. Results The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. Conclusions We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

scholarly journals Da-Bu-Yin-Wan and Qian-Zheng-San to Neuroprotect the Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Gang Gong ◽  
Hong-Mei Sun ◽  
Yi Zhang ◽  
Shu-Jing Zhang ◽  
Yu-Shan Gao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neuroprotective Effect ◽  
Firefly Luciferase ◽  
Dopamine Neurons ◽  
Behavioral Impairment ◽  
Neuroprotective Effects ◽  
Atp Level ◽  
Protein Levels

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson’s disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATPchannel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATPchannel subunit expressions.

scholarly journals Salidroside Protects Dopaminergic Neurons by Enhancing PINK1/Parkin-Mediated Mitophagy

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Ruru Li ◽  
Jianzong Chen
Keyword(s):  
Dopaminergic Neurons ◽  
Complex I ◽  
Neuroprotective Effect ◽  
Motor Deficits ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Cytoprotective Effect ◽  
Neuroprotective Effects ◽  
Mn9d Cells ◽  
Complex I Activity

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the degeneration of nigrostriatal dopaminergic (DA) neurons. Our previous studies have suggested that salidroside (Sal) might play neuroprotective effects against PD by preserving mitochondrial Complex I activity. However, the exact mechanism of the neuroprotective effect of Sal remains unclear. Growing evidence indicates that PINK1/Parkin-mediated mitophagy is involved in the development of PD. In this study, we investigated whether Sal exerts a neuroprotective effect by modulating PINK1/Parkin-mediated mitophagy. Results showed that Sal alleviated MPTP-induced motor deficits in pole test. Moreover, Sal diminished MPTP-induced degeneration of nigrostriatal DA neurons as evidenced by upregulated TH-positive neurons in the substantia nigra, increased DAT expression, and high dopamine and metabolite levels in the striatum. Furthermore, in comparison with the MPP+/MPTP group, Sal considerably increased the mitophagosome and mitophagy flux. Moreover, in comparison with the MPP+/MPTP group, Sal evidently enhanced the mitochondrial expression of PINK1 and Parkin, accompanied by an increase in the colocalization of mitochondria with Parkin. However, transfection of MN9D cells with PINK1 siRNA reversed Sal-induced activated mitophagy and cytoprotective effect. In conclusion, Sal may confer neuroprotective effects by enhancing PINK1/Parkin-mediated mitophagy in MPP+/MPTP-induced PD models.

scholarly journals Shenxiong Drop Pill exerts neuroprotective effect against focal cerebral ischemia partly via regulation of the expressions of ICAM-1 and caspase-3

2021 ◽  
Vol 20 (10) ◽  
pp. 2015-2022
Author(s):  
Shuo-guo Jin ◽  
Ze-ran Chen ◽  
Yang Zhang ◽  
Meng-yuan Huang ◽  
Meng Hou ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Caspase 3 ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Triphenyltetrazolium Chloride ◽  
Scoring Method ◽  
Nissl Staining ◽  
Neuroprotective Effects

Purpose: To investigate the effect of Shenxiong Drop Pill (SXDP) on cerebral infarction (CI) in rats, and the involvement of anti-inflammatory response in the process.Methods: Rats were sacrificed at three different time points, viz, 24, 48 and 72 h after establishment of CI model. Neurological deficit score (NDS) was determined using Bederson’s neurological behavioral scoring method, whereas triphenyltetrazolium chloride (TTC) staining was used to show brain injury. The integrated optical density (IOD) of Nissl bodies and caspase-3-positive nerve cells were measured with Nissl staining and SP kit, respectively. The mRNA expression of intercellular adhesion molecule 1(ICAM-1) was determined using reverse transcription-polymerase chain reaction (RT-PCR).Results: SXDP produced neuroprotective effect at high, medium, and low doses. The infarct volumes in the high-, medium- and low-dose SXDP, and cyclophosphamide groups were significantly reduced at each time point. Different doses of SXDP significantly reduced the mRNA expression of ICAM-1 and the IOD of caspase-3.Conclusion: These results indicate that SXDP exerts neuroprotective effects against ischemic injury by negatively regulating ICAM-1/caspase-3 downstream of inflammatory and apoptosis pathways.

scholarly journals Neuroprotectionby MK-801 following cerebral ischemia in Mongolian gerbils

2008 ◽  
Vol 60 (3) ◽  
pp. 341-346 ◽  
Author(s):  
Lidija Radenovic ◽  
Vesna Selakovic ◽  
P.R. Andjus
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Neuronal Loss ◽  
Brain Structures ◽  
Cell Loss ◽  
Global Cerebral Ischemia ◽  
Mongolian Gerbils ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Mk 801

Global cerebral ischemia in Mongolian gerbils is an established model in experimental research on cerebral ischemia, which is characterized morphologically by selective neuronal damage in the hippocampus, striatum, and cortex. Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of dizocilpine malate (MK-801), a non-competitive glutamate antagonist, in the model of 10-min gerbil cerebral ischemia. Gerbils were given MK-801(3 mg/kg i.p.)or saline immediately after the occlusion. On day 4 after reperfusion, neuronal damage was examined in the hippocampus (30 ?m)and striatum slices (5 ?m)stained with hematoxylin/eosin, fluorescent Nissl staining and membrane tracer DiI. The striatum and C3 regions of the hippocampus were analyzed by confocal microscopy. Neuroprotection was determined by quantifying the degree of cell loss, reduction of morphologically damaged cells, and the degree of preservation of recog?nizable neuroanatomical pathways after the ischemic insult. Our results demonstrate that the neuronal damage induced by sustained ischemia is related to abnormalities in glutamatergic function associated with NMDA receptors. MK-801significantly prevented neuronal loss in the tested brain structures. All of this contributes to a better understanding of the given pathophysiological process causing ischemic neuronal damage. <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/ABS160524054E">10.2298/ABS160524054E</a><u></b></font>

scholarly journals The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury

2020 ◽  
Author(s):  
Chung-Che Lu ◽  
Che-Chuan Wang ◽  
Yao-Lin Lee ◽  
Chung-Ching Chio ◽  
Sher-Wei Lim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Nitrosative Stress ◽  
Neuroprotective Effect ◽  
Acute Stage ◽  
Motor Deficits ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Infarction Volume

Abstract The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.

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