scholarly journals In vitroscreening of neuroprotective activity of Indian medicinal plantWithania somnifera

2017 ◽  
Vol 6 ◽  
Author(s):  
Manjeet Singh ◽  
Charles Ramassamy
Keyword(s):  
Neuroblastoma Cell ◽  
Amyloid Β ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Activity ◽  
Great Promise ◽  
Human Neuroblastoma Cell ◽  
Amyloid Β Peptide ◽  
Aβ Peptide ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma

AbstractCanine cognitive dysfunction (CCD) is an age-dependent neurodegenerative condition characterised by changes in decline in learning and memory patterns. The neurodegenerative features of CCD in ageing dogs and cats are similar to human ageing and Alzheimer's disease (AD). Discovering neuroprotective disease-modifying therapies against CCD and AD is a major challenge. Strong evidence supports the role of amyloid β peptide deposition and oxidative stress in the pathophysiology of CCD and AD. In both the human and canine brain, oxidative damage progressively increases with age. Dietary antioxidants from natural sources hold a great promise in halting the progression of CCD and AD.Withania somnifera(WS), an Ayurvedic tonic medicine, also known as ‘Indian ginseng’ orashwagandhahas a long history of use in memory-enhancing therapy but there is a dearth of studies on its neuroprotective effects. The objective of this study was to investigate whetherWSextract can protect against Aβ peptide- and acrolein-induced toxicity. We demonstrated that treatment withWSextract significantly protected the human neuroblastoma cell line SK-N-SH against Aβ peptide and acrolein in various cell survival assays. Furthermore, treatment withWSextract significantly reduced the generation of reactive oxygen species in SK-N-SH cells. Finally, our results showed thatWSextract is also a potent inhibitor of acetylcholinesterase activity. Thus, our initial findings indicate thatWSextract may act as an antioxidant and cholinergic modulator and may have beneficial effects in CCD and AD therapy.

scholarly journals The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Chol Seung Lim ◽  
Jung-Soo Han
Keyword(s):  
Therapeutic Potential ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Enzymatic Activities ◽  
Oxidative Modification ◽  
Amyloid Β Peptide ◽  
Oxygen Species ◽  
Human Neuroblastoma Cells ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP activities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.

scholarly journals PI3K activation prevents Aβ42-induced synapse loss and favors insoluble amyloid deposits formation

2019 ◽  
Author(s):  
Mercedes Arnés ◽  
Ninovska Romero ◽  
Sergio Casas-Tintó ◽  
Ángel Acebes ◽  
Alberto Ferrús
Keyword(s):  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Synapse Loss ◽  
Amyloid Deposits ◽  
Pi3k Activation ◽  
Aβ42 Peptide

AbstractAlzheimer’s disease is, to a large extent, a disease of the synapse triggered by the unbalanced amyloidogenic cleavage of the amyloid precursor protein APP. Excess of Aβ42 peptide in particular is considered a hallmark of the disease. Here we drive the expression of the human Aβ42 peptide to assay the neuroprotective effects of PI3K in adult Drosophila melanogaster. We show that the neuronal expression of the human peptide elicits progressive toxicity in the adult. The pathological traits include reduced axonal transport, synapse loss, defective climbing ability and olfactory perception, as well as life-span reduction. The Aβ42-dependent synapse decay does not involve transcriptional changes in the core synaptic protein encoding genes: bruchpilot, liprin and synaptobrevin. All toxicity features, however, are suppressed by the co-expression of PI3K. Moreover, PI3K activation induces a significant increase of 6E10 and Thioflavin-positive amyloid deposits. Mechanistically, we suggest that Aβ42-Ser26 could be a candidate residue for direct or indirect phosphorylation by PI3K. Finally, along with these in vivo experiments we further analyze Aβ42 toxicity and its suppression by PI3K activation in in vitro assays with SH-SY5Y human neuroblastoma cell cultures, where Aβ42 aggregation into large insoluble deposits is reproduced. Taken together, these results uncover a potential novel pharmacological strategy against this disease with PI3K activation as a target.

scholarly journals IRE1α-XBP1 Affects the Mitochondrial Function of Aβ25–35-Treated SH-SY5Y Cells by Regulating Mitochondria-Associated Endoplasmic Reticulum Membranes

2021 ◽  
Vol 15 ◽  
Author(s):  
Bingcong Chu ◽  
Maoyu Li ◽  
Xi Cao ◽  
Rulong Li ◽  
Suqin Jin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mitochondrial Dysfunction ◽  
Calcium Imaging ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Aβ Peptide ◽  
Human Neuroblastoma ◽  
New Treatment

Background: Neurotoxicity induced by the amyloid beta (Aβ) peptide is one of the most important pathological mechanisms of Alzheimer's disease (AD). Activation of the adaptive IRE1α-XBP1 pathway contributes to the pathogenesis of AD, making it a potential target for AD therapeutics. However, the mechanism of IRE1α-XBP1 pathway involvement in AD is unclear. We, therefore, investigated the effect of the IRE1α-XBP1 axis in an in vitro AD model and explored its potential mechanism.Methods: The human neuroblastoma cell line, SH-SY5Y, was used. Cells were treated with Aβ25–35, with or without 4μ8c, an inhibitor of IRE1α. Cells were collected and analyzed by Western blotting, quantitative real-time PCR, electron microscopy, fluorescence microscopy, calcium imaging, and other biochemical assays.Results: Aβ-exposed SH-SY5Y cells showed an increased expression of XBP1s and p-IRE1α. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and calcium imaging analysis showed that the IRE1α inhibitor, 4μ8c, reduced Aβ-induced cytotoxicity. Increased levels of ATP, restoration of mitochondrial membrane potential, and decreased production of mitochondrial reactive oxygen species after Aβ treatment in the presence of 4μ8c showed that inhibiting the IRE1α-XBP1 axis effectively mitigated Aβ-induced mitochondrial dysfunction in SH-SY5Y cells. Furthermore, Aβ treatment increased the expression and interaction of IP3R, Grp75, and vdac1 and led to an increased endoplasmic reticulum (ER)–mitochondria association, malfunction of mitochondria-associated ER-membranes (MAMs), and mitochondrial dysfunction. These deficits were rescued by inhibiting the IRE1α-XBP1 axis.Conclusion: These findings demonstrate that Aβ peptide induces the activation of the IRE1α-XBP1 axis, which may aggravate cytotoxicity and mitochondrial impairment in SH-SY5Y cells by targeting MAMs. Inhibition of the IRE1α-XBP1 axis provides the protection against Aβ-induced injury in SH-SY5Y cells and may, therefore, be a new treatment strategy.

Design, Synthesis and Evaluation of 8-Thiosubstituted 1,3,7- Trimethylxanthine Hydrazones with In-vitro Neuroprotective and MAO-B Inhibitory Activities

2020 ◽  
Vol 16 (3) ◽  
pp. 326-339 ◽  
Author(s):  
Javor Mitkov ◽  
Alexandra Kasabova-Angelova ◽  
Magdalena Kondeva-Burdina ◽  
Virginia Tzankova ◽  
Diana Tzankova ◽  
...  
Keyword(s):  
Biological Activities ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Significant Activity ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Mao B ◽  
Chemical Structures

Objective:The syntheses and biological activities of 8-thiosubstituted-1,3,7- trimethylxanthine derivatives bearing an aromatic hydrazide-hydrazone fragment in the side chain at C8 are described.Methods:The chemical structures of the synthesized compounds 6a-m were confirmed based on their MS, FTIR, 1H NMR and 13C NMR analyses.Results:The in vitro investigations of neuroprotective effects manifested on cellular (human neuroblastoma cell line SH-SY5Y) and sub-cellular (isolated rat brain synaptosomes) levels show that compounds 6g and 6i demonstrate statistically significant activity. The performed monoamine oxidase B (MAO-B) inhibition study in vitro show that compounds 6g and 6i possess a significant MAO-B inhibition activity close to L-deprenyl.Conclusion:These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for the treatment of Parkinson’s disease.

SuHeXiang Wan Essential Oil Alleviates Amyloid Beta Induced Memory Impairment Through Inhibition of Tau Protein Phosphorylation in Mice

2011 ◽  
Vol 39 (05) ◽  
pp. 917-932 ◽  
Author(s):  
Songhee Jeon ◽  
Jinyoung Hur ◽  
Ha Jin Jeong ◽  
Byung-Soo Koo ◽  
Sok Cheon Pak
Keyword(s):  
Essential Oil ◽  
Memory Impairment ◽  
Neuroblastoma Cell ◽  
Amyloid Β ◽  
Control Group ◽  
Human Neuroblastoma Cell ◽  
Amyloid Β Protein ◽  
Human Neuroblastoma ◽  
In Vitro Investigation

SuHeXiang Wan (SHXW), a traditional Chinese medicine, has been used orally for the treatment of seizures, infantile convulsions and stroke. Previously, we reported the effects of a modified SHXW essential oil in terms of sedative effect, anticonvulsant activity and antioxidative activity. The purpose of this study was to evaluate the potential beneficial effects of SHXW essential oil in neurodegenerative diseases such as Alzheimer's disease (AD). SHXW essential oil was extracted from nine herbs. The mouse AD model was induced by a single injection of amyloid β protein (Aβ1-42) into the hippocampus. The animals were divided into four groups, the negative control group injected with Aβ42-1, the Aβ group injected with Aβ1-42, the SHXW group inhaled SHXW essential oil and received Aβ1-42 injection, and the positive control group administered with docosahexaenoic acid (DHA, 10 mg/kg) and with subsequent Aβ1-42 injection. Mice were analyzed by behavioral tests and immunological examination in the hippocampus. An additional in vitro investigation was performed to examine whether SHXW essential oil inhibits Aβ1-42 induced neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells. Pre-inhalation of SHXW essential oil improved the Aβ1-42 induced memory impairment and suppressed Aβ1-42 induced JNK, p38 and Tau phosphorylation in the hippocampus. SHXW essential oil suppressed Aβ-induced apoptosis and ROS production via an up-regulation of HO-1 and Nrf2 expression in SH-SY5Y cells. The present study suggests that SHXW essential oil may have potential as a therapeutic inhalation drug for the prevention and treatment of AD.

scholarly journals The Neuroprotective Effects of Astragaloside IV against H2O2-Induced Damage in SH-SY5Y Cells are Associated with Synaptic Plasticity

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Zurong Song ◽  
Ali Tao
Keyword(s):  
Synaptic Plasticity ◽  
Western Blot ◽  
Cell Viability ◽  
Cell Damage ◽  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Protective Effects ◽  
Astragaloside Iv ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma

The aim of this study was to investigate whether the neuroprotective effects of astragaloside IV (AS-IV) against hydrogen peroxide (H2O2)-induced damage on human neuroblastoma cell line (SH-SY5Y) are associated with synaptic plasticity. The concentration screening of AS-IV and H2O2 on SH-SY5Y cells and the protective effects of AS-IV on SH-SY5Y cells under H2O2 stress were all determined by MTT assay. The expression of postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were measured by western blot (WB) and inmunofluorescence staining assay under the same treatment conditions. According to the MTT results, the concentration of H2O2 at 50 μmol/L for 3 h was used for the cell damage model, and various concentrations of AS-IV (0.1, 0.2, 0.3, and 0.4 μmol/L) were used to affect SH-SY5Y cells. The MTT results showed that pretreatment of SH-SY5Y cells with AS-IV (0.1, 0.2, 0.3, and 0.4 μmol/L) attenuated the damage induced by H2O2 (50 μmol/L, 51.62% cell viability) and increased cell viability to 64.19, 63.48, 65.86, and 65.81%, respectively. Western blot analysis and immunofluorescence staining showed that the protective effects of AS-IV against SH-SY5Y cell damage caused by H2O2 resulted in reduced expression of PSD-95 and increased expression of GAP-43 in comparison with the H2O2 treatment group. The conclusion shows that AS-IV protected SH-SY5Y cells and enhanced their viability under H2O2 stress. AS-IV may facilitate presynaptic and postsynaptic plasticity to exert protective effects against oxidative damage of SH-SY5Y cells.

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