scholarly journals Preparation, Optimization and Evaluation of Chitosan-Based Avanafil Nanocomplex Utilizing Antioxidants for Enhanced Neuroprotective Effect on PC12 Cells

Gels ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 96
Author(s):  
Mallesh Kurakula ◽  
Raghavendra Naveen N. ◽  
Bhaumik Patel ◽  
Ravi Manne ◽  
Devang B. Patel
Keyword(s):  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Precipitation Method ◽  
Natural Polymers ◽  
High Solubility ◽  
Box Behnken Design ◽  
Neuroprotective Strategy ◽  
Optimum Formulation ◽  
Desirability Approach

(1) Introduction: in recent decades, interdisciplinary research on the utilization of natural products as “active moiety carriers” was focused on due to their superior safety profile, biodegradability, biocompatibility and the ability for sustained or controlled release activity. The nano-based neuroprotective strategy is explored as an imperative treatment for diabetic neuropathy (DN). Avanafil (AV), that selectively inhibits the degradation of cGMP-specific phosphodiesterase, thereby increasing the levels of cGMP, makes a decisive mediator for cytoprotection. (2) Methods: AVnanocomplex formulations were prepared by a modified anti-solvent precipitation method and the method was optimized by Box–Behnken design. An optimized formulation was characterized and evaluated for various in vitro parameters; (3) results:based on the desirability approach, the formulation containing 2.176 g of chitosan, 7.984 g of zein and 90% v/v ethanol concentration can fulfill the prerequisites of optimum formulation (OB-AV-NC).OB-AV-NC was characterized and evaluated for various parameters. The neuroprotective mechanism of AV was evaluated by pretreatment of PC12 cells with plain AV, avanafil nanocomplex (NC) without antioxidants (AV-NC) and with antioxidants (α-Lipoic acid LP; Ellagic Acid EA), AV-LP-EA-Nanocomplex has also shown considerable attenuation in intracellular reactive oxygen species (ROS) and lipid peroxidation with a significant increase in the PC 12 viability under HG conditions in comparison to pure AV; (4) conclusion: the nanocomplex of AV prepared to utilize natural polymers and antioxidants aided for high solubility of AV and exhibited desired neuroprotective activity.This can be one of the promisingstrategy to translate the AV nanocomplex with safety and efficacy in treating DN.

scholarly journals Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Fang Xian ◽  
Zhi-Xiu Lin ◽  
Qing-Qiu Mao ◽  
Jian-Nan Chen ◽  
Zi-Ren Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Protective Effects ◽  
Phosphorylated Akt ◽  
Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

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

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.

The Neuroprotective Effect of Picroside II from Hu-Huang-Lian against Oxidative Stress

2007 ◽  
Vol 35 (04) ◽  
pp. 681-691 ◽  
Author(s):  
Ting Li ◽  
Jian-Wen Liu ◽  
Xiao-Dong Zhang ◽  
Ming-Chuan Guo ◽  
Guang Ji
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Active Constituent ◽  
Sod Activity ◽  
Picroside Ii ◽  
Pre Treatment

Picroside II is an active constituent extracted from the traditional Chinese medicine (TCM) Hu-Huang-Lian. To evaluate the neuroprotective effect of picroside II, PC12 cells were treated with glutamate in vitro and male ICR mice were treated with AlCl 3in vivo. Pre-treatment of PC12 cells with picroside II could enhance the cell viability and decrease the level of intracellular reactive oxygen species (ROS) induced by glutamate. By DNA fragmentation and flow cytometry assay, picroside II (1.2 mg/ml) significantly prevented glutamate-induced cell apoptosis. In the animal study, amnesia was induced in mice by AlCl 3 (100 mg/kg/d, i.v.). Pricroside II, at the dose of 20 and 40 mg/kg/d (i.g.), markedly ameliorated AlCl 3-induced learning and memory dysfunctions and attenuated AlCl 3-induced histological changes. This was associated with the significant increased superoxide dismutase (SOD) activity in the brain of experimental mice. All these results indicated that picroside II possessed the therapeutic potential in protecting against neurological injuries damaged by oxidative stress.

scholarly journals Shenzhi Jiannao formula ameliorates vascular dementia in vivo and in vitro by inhibition glutamate neurotoxicity via promoting clathrin-mediated endocytosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Danfeng Tian ◽  
Yangyang Guo ◽  
Dandan Zhang ◽  
Qiang Gao ◽  
Ganlu Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Vascular Dementia ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Glutamate Excitotoxicity ◽  
Mrna Levels ◽  
Neuroprotective Effects ◽  
Promising Alternative

Abstract Background Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B and N-methyl-d-aspartic acid receptor 1 (NMDAR1) proteins play a vital role in endocytosis of synaptic vesicles in neurons and glutamate over accumulation. Previous researches have been confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic and neuroprotective effect in VD, but the underlying mechanisms are still unclear. In this study, we aimed to explore the effect of SZJN formula on cognitive impairment and glutamate excitotoxicity via clathrin-mediated endocytosis (CME) in vivo and in vitro. Methods SZJN formula consists of Panax ginseng C.A.Mey., Anemarrhena asphodeloides Bunge, and Paeonia anomala subsp. veitchii (Lynch) D.Y.Hong & K.Y.Pan. All herbs were prepared into granules. Both common carotid arteries were permanent occluded (2‐vessel occlusion, 2VO) in male Sprague Dawley (SD) rats to model VD. One day after operation, the rats began daily treatment with SZJN formula for 2 weeks. The neuroprotective effects of SZJN formula was subsequently assessed by the novel object recognition test, Morris water maze, hematoxylin–eosin (HE) staining and Nissl staining. Glutamate cytotoxicity was assessed by detecting cell viability and cell death of PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, and quantitative real‐time PCR were used to detect the expression levels of clathrin, RAB5B, and NMDAR1. Results Administration of SZJN formula effectively improved short-term memory and spatial memory. SZJN formula treatment significantly reduced hippocampal neuronal loss, and recovered the arrangement and morphology of neurons and Nissl bodies. Moreover, SZJN formula promoted the proliferation of PC12 cells and inhibited glutamate-induced cell death. The down-regulation of clathrin and RAB5B, as well as the upregulation of NMDAR1 in the brain induced by 2VO or glutamate was also notably reversed by SZJN formula at both the protein and mRNA levels, which may contribute to SZJN formula induced improved neurological function. Conclusions Taken together, our findings provide evidence that the neuroprotective effects of SZJN formula in experimental VD maybe mediated through promoting the expression of clathrin-mediated endocytosis and reducing NMDARs‐associated glutamate excitotoxicity. SZJN formula serves as a promising alternative therapy and may be a useful herbal medicine for preventing progression of VD. Graphic abstract

scholarly journals Exploring the Mechanism of Panax notoginseng Saponins against Alzheimer’s Disease by Network Pharmacology and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yixuan Jiang ◽  
Shanliang Li ◽  
Xiaoqin Xie ◽  
Hemei Li ◽  
Panling Huang ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Panax Notoginseng ◽  
Network Pharmacology ◽  
Protective Effects ◽  
Panax Notoginseng Saponins ◽  
Active Ingredients ◽  
Target Disease ◽  
And Function

Background. Panax notoginseng saponins (PNS) have been used for neurodegenerative disorders such as cerebral ischemia and Alzheimer’s disease (AD). Although increasing evidences show the neuron protective effects of PNS, the vital compounds and their functional targets remain elusive. To explore the potential functional ingredients of PNS for the AD treatment and their molecular mechanisms, an in vitro neuron injured model induced by Aβ was investigated, and the potential mechanism was predicted by network pharmacology approach and validated by molecular biology methods. Methods. Network pharmacology approach was used to reveal the relationship between ingredient-target disease and function-pathway of PNS on the treatment of AD. The active ingredients of PNS were collected from TCMSP, PubChem database, and literature mining in PubMed database. DrugBank and GeneCards database were used to predict potential targets for AD. The STRING database was performed to reveal enrichment of these target proteins, protein-protein interactions, and related pathways. Networks were visualized by utilizing Cytoscape software. The enrichment analysis was performed by the DAVID database. Finally, neuroprotective effect and predictive mechanism of PNS were investigated in an in vitro AD model established by Aβ25–35-treated PC12 cells. Results. An ingredient-target disease and function-pathway network demonstrated that 38 active ingredients were derived from PNS modulated 364 common targets shared by PNS and AD. GO and KEGG analysis, further clustering analysis, showed that mTOR signaling targets were associated with the neuroprotective effects of PNS. In Aβ-treated PC12 cells, PNS treatment improved neuroprotective effect, including mTOR inhibition and autophagy activation. Conclusions. Collectively, the protective effects of PNS on AD-neuron injury are related to the inhibition of mTOR and autophagy activation.

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

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.

In vitro evaluation of the neuroprotective effect of oligo-porphyran from Porphyra yezoensis in PC12 cells

2019 ◽  
Vol 31 (4) ◽  
pp. 2559-2571 ◽  
Author(s):  
YingJuan Liu ◽  
Zhenzhen Deng ◽  
Lihua Geng ◽  
Jing Wang ◽  
Quanbin Zhang
Keyword(s):  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Porphyra Yezoensis ◽  
In Vitro Evaluation

scholarly journals The Aqueous Extract of Rhizome ofGastrodia elataProtectedDrosophilaand PC12 Cells against Beta-Amyloid-Induced Neurotoxicity

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chun-Fai Ng ◽  
Chun-Hay Ko ◽  
Chi-Man Koon ◽  
Jia-Wen Xian ◽  
Ping-Chung Leung ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Aqueous Extract ◽  
Neuroprotective Effect ◽  
Beta Amyloid ◽  
Current Data ◽  
Dependent Manner ◽  
Amyloid A ◽  
Apoptotic Marker

This study aims to investigate the neuroprotective effect of the rhizome ofGastrodia elata(GE) aqueous extract on beta-amyloid(Aβ)-induced toxicityin vivoandin vitro. TransgenicDrosophilamutants with Aβ-induced neurodegeneration in pan-neuron and ommatidia were used to determine the efficacy of GE. The antiapoptotic and antioxidative mechanisms of GE were also studied in Aβ-treated pheochromocytoma (PC12) cells.In vivostudies demonstrated that GE (5 mg/gDrosophilamedia)-treatedDrosophilapossessed a longer lifespan, better locomotor function, and less-degenerated ommatidia when compared with the Aβ-expressing control (allP<0.05).In vitrostudies illustrated that GE increased the cell viability of Aβ-treated PC12 cells in dose-dependent manner, probably through attenuation of Aβ-induced oxidative and apoptotic stress. GE also significantly upregulated the enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase, leading to the decrease of reactive oxidation species production and apoptotic marker caspase-3 activity. In conclusion, our current data presented the first evidence that the aqueous extract of GE was capable of reducing the Aβ-induced neurodegeneration inDrosophila, possibly through inhibition of apoptosis and reduction of oxidative stress. GE aqueous extract could be developed as a promising herbal agent for neuroprotection and novel adjuvant therapies for Alzheimer’s disease.

scholarly journals Neuroprotective Effect of Dioscin on the Aging Brain

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1247 ◽  
Author(s):  
Yan Qi ◽  
Ruomiao Li ◽  
Lina Xu ◽  
Lianhong Yin ◽  
Youwei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Protein Carbonyl ◽  
Learning Ability ◽  
Aging Brain ◽  
Protein Carbonyl Content

Our previous works have shown that dioscin, a natural product, has various pharmacological activities, however, its role in brain aging has not been reported. In the present study, in vitro H2O2-treated PC12 cells and in vivo d-galactose-induced aging rat models were used to evaluate the neuroprotective effect of dioscin on brain aging. The results showed that dioscin increased cell viability and protected PC12 cells against oxidative stress through decreasing reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels. In vivo, dioscin markedly improved the spatial learning ability and memory of aging rats, reduced the protein carbonyl content and aging cell numbers, restored the levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and nitric oxide synthase (NOS) in brain tissue, and reversed the histopathological structure changes of nerve cells. Mechanism studies showed that dioscin markedly adjusted the MAPK and Nrf2/ARE signalling pathways to decrease oxidative stress. Additionally, dioscin also significantly decreased inflammation by inhibiting the mRNA or protein levels of TNF-α, IL-1β, IL-6, CYP2E1 and HMGB1. Taken together, these results indicate that dioscin showed neuroprotective effect against brain aging via decreasing oxidative stress and inflammation, which should be developed as an efficient candidate in clinical to treat brain aging in the future.

scholarly journals Shenzhi Jiannao Formula Ameliorates Vascular Dementia in Vivo and in Vitro by Inhibition Glutamate Neurotoxicity via Promoting Clathrin-Mediated Endocytosis

2021 ◽  
Author(s):  
Danfeng Tian ◽  
Yangyang Guo ◽  
Dandan Zhang ◽  
Qiang Gao ◽  
Ganlu Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Vascular Dementia ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Glutamate Excitotoxicity ◽  
Mrna Levels ◽  
Neuroprotective Effects ◽  
Promising Alternative

Abstract Background: Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B and N-methyl-d-aspartic acid receptor 1 (NMDAR1) proteins play a vital role in endocytosis of synaptic vesicles in neurons and glutamate over accumulation. Previous researches have been confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic and neuroprotective effect in VD, but the underlying mechanisms are still unclear. In this study, we aimed to explore the effect of SZJN formula on cognitive impairment and glutamate excitotoxicity via clathrin-mediated endocytosis (CME) in vivo and in vitro. Methods: Both common carotid arteries were permanent occluded (2‐vessel occlusion, 2VO) in male Sprague Dawley (SD) rats to model VD. One day after operation, the rats began daily treatment with SZJN formula for two weeks. The neuroprotective effects of SZJN formula was subsequently assessed by the novel object recognition test, Morris water maze, hematoxylin-eosin (HE) staining and Nissl staining. Glutamate cytotoxicity was assessed by detecting cell viability and cell death of PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, and quantitative real‐time PCR were used to detect the expression levels of clathrin, RAB5B, and NMDAR1.Results: Administration of SZJN formula effectively improved short-term memory and spatial memory. SZJN treatment significantly reduced hippocampal neuronal loss, and recovered the arrangement and morphology of neurons and Nissl bodies. Moreover, SZJN formula promoted the proliferation of PC12 cells and inhibited glutamate-induced cell death. The down-regulation of clathrin and RAB5B, as well as the upregulation of NMDAR1 in the brain induced by 2VO or glutamate was also notably reversed by SZJN formula at both the protein and mRNA levels, which may contribute to SZJN formula induced improved neurological function. Conclusions: Taken together, our findings provide evidence that the neuroprotective effects of SZJN formula in experimental VD maybe mediated through promoting the expression of clathirn-mediated endocytosis and reducing NMDARs‐associated glutamate excitotoxicity. SZJN formula serves as a promising alternative therapy and may be a useful herbal medicine for preventing progression of VD.

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