Berberine nanoencapsulation attenuates hallmarks of scoplomine induced Alzheimer's-like disease in rats

2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Histopathological Examination ◽  
Memory Function ◽  
Amyloid Β ◽  
Active Pharmaceutical Ingredient ◽  
Isoquinoline Alkaloid ◽  
Drug Uptake ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.

scholarly journals Neuroprotective effects of verbascoside against Alzheimer’s disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chunyue Wang ◽  
Xueying Cai ◽  
Ruochen Wang ◽  
Siyu Zhai ◽  
Yongfeng Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Amyloid Β ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Morris Water Maze Test ◽  
Proteomics Analysis ◽  
Neuroprotective Effects ◽  
U251 Cells

Abstract Background Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods U251 cells were co-incubated with 10 μM of Aβ1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ1-42-damaged U251 cells. Results In Aβ1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.

scholarly journals LongShengZhi Capsule Attenuates Alzheimer-Like Pathology in APP/PS1 Double Transgenic Mice by Reducing Neuronal Oxidative Stress and Inflammation

2020 ◽  
Vol 12 ◽  
Author(s):  
Zequn Yin ◽  
Xuerui Wang ◽  
Shihong Zheng ◽  
Peichang Cao ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
B Cell Lymphoma ◽  
Acanthopanax Senticosus ◽  
Neuroprotective Effects ◽  
Long Term Treatment ◽  
Double Transgenic Mice ◽  
The Brain

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It may be caused by oxidative stress, inflammation, and cerebrovascular dysfunctions in the brain. LongShengZhi Capsule (LSZ), a traditional Chinese medicine, has been approved by the China Food and Drug Administration for treatment of patients with cardiovascular/cerebrovascular disease. LSZ contains several neuroprotective ingredients, including Hirudo, Astmgali Radix, Carthami Flos (Honghua), Persicae Semen (Taoren), Acori Tatarinowii Rhizoma (Shichangpu), and Acanthopanax Senticosus (Ciwujia). In this study, we aimed to determine the effect of LSZ on the AD process. Double transgenic mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1) to model AD were treated with LSZ for 7 months starting at 2 months of age. LSZ significantly improved the cognition of the mice without adverse effects, indicating its high degree of safety and efficacy after a long-term treatment. LSZ reduced AD biomarker Aβ plaque accumulation by inhibiting β-secretase and γ-secretase gene expression. LSZ also reduced p-Tau expression, cell death, and inflammation in the brain. Consistently, in vitro, LSZ ethanol extract enhanced neuronal viability by reducing L-glutamic acid-induced oxidative stress and inflammation in HT-22 cells. LSZ exerted antioxidative effects by enhancing superoxide dismutase and glutathione peroxidase expression, reduced Aβ accumulation by inhibiting β-secretase and γ-secretase mRNA expression, and decreased p-Tau level by inhibiting NF-κB-mediated inflammation. It also demonstrated neuroprotective effects by regulating the Fas cell surface death receptor/B-cell lymphoma 2/p53 pathway. Taken together, our study demonstrates the antioxidative stress, anti-inflammatory, and neuroprotective effects of LSZ in the AD-like pathological process and suggests it could be a potential medicine for AD treatment.

scholarly journals The Neuroprotective Effects of Carvacrol on Ethanol-Induced Hippocampal Neurons Impairment via the Antioxidative and Antiapoptotic Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Peng Wang ◽  
Qian Luo ◽  
Hui Qiao ◽  
Hui Ding ◽  
Yonggang Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Morris Water Maze Test ◽  
Oxidative Stress Biomarkers ◽  
Neuroprotective Effects ◽  
Stress Injury

Chronic alcohol consumption causes hippocampal neuronal impairment, which is associated with oxidative stress and apoptosis. Carvacrol is a major monoterpenic phenol found in essential oils from the family Labiatae and has antioxidative stress and antiapoptosis actions. However, the protective effects of carvacrol in ethanol-induced hippocampal neuronal impairment have not been fully understood. We explored the neuroprotective effects of carvacrol in vivo and in vitro. Male C57BL/6 mice were exposed to 35% ethanol for 4 weeks to establish ethanol model in vivo, and hippocampal neuron injury was simulated by 200 mM ethanol in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. The oxidative stress injury of hippocampal neurons was evaluated by measuring the levels of oxidative stress biomarkers. Histopathological examinations and western blot were performed to evaluate the apoptosis of neurons. The results showed that carvacrol attenuates the cognitive dysfunction, oxidative stress, and apoptosis of the mice treated with ethanol and decreases hippocampal neurons apoptosis induced by ethanol in vitro. In addition, western blot analysis revealed that carvacrol modulates the protein expression of Bcl-2, Bax, caspase-3, and p-ERK, without influence of p-JNK and p-p38. Our results suggest that carvacrol alleviates ethanol-mediated hippocampal neuronal impairment by antioxidative and antiapoptotic effects.

Neuroprotective effects of N-adamantyl-4-methylthiazol-2-amine against amyloid β-induced oxidative stress in mouse hippocampus

2017 ◽  
Vol 128 ◽  
pp. 22-28 ◽  
Author(s):  
Jiae Kim ◽  
Chang Hun Cho ◽  
Hoh-Gyu Hahn ◽  
Soo-Young Choi ◽  
Sung-Woo Cho
Keyword(s):  
Oxidative Stress ◽  
Amyloid Β ◽  
Neuroprotective Effects ◽  
Mouse Hippocampus

scholarly journals Neuroprotective Effects of Black Pepper Cold-Pressed Oil on Scopolamine-Induced Oxidative Stress and Memory Impairment in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1993
Author(s):  
Nada M. Mostafa ◽  
Ahmed M. Mostafa ◽  
Mohamed L. Ashour ◽  
Sameh S. Elhady
Keyword(s):  
Oxidative Stress ◽  
Black Pepper ◽  
Morris Water Maze Test ◽  
Piper Nigrum ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Reference Drug ◽  
Monoterpene Hydrocarbons ◽  
Cold Pressed ◽  
The Impact

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.

scholarly journals Does ( −)-epigallocatechin-3-gallate protects the neurotoxicity induced by bisphenol A in vivo?

2022 ◽  
Author(s):  
Manar Mohammed El Tabaa ◽  
Samia Salem Sokkar ◽  
Ehab Sayed Ramdan ◽  
Inas Zakria Abd El Salam ◽  
Anis Anis
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Histopathological Examination ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Neuroprotective Effects ◽  
Hippocampal Ca3 ◽  
Ca3 Neurons ◽  
Potential Efficiency

AbstractBisphenol A (BPA) is one of the chemicals that is firmly accompanied by hippocampal neuronal injury. As oxidative stress appears to be a major contributor to neurotoxicity induced by BPA, antioxidants with remarkable neuroprotective effects can play a valuable protective role. Around the world, ( −)-epigallocatechin-3-gallate (EGCG) was one of the most popular antioxidants that could exert a beneficial neuroprotective role. Here, we examined the potential efficiency of EGCG against neurotoxicity induced by BPA in the hippocampal CA3 region of the rat model. This study revealed that EGCG was unable to abrogate the significant decrease in circulating adiponectin level and hippocampal superoxide dismutase activity as well as an increase in hippocampal levels of nitric oxide and malondialdehyde. Notably, EGCG failed to antagonize the oxidative inhibitory effect of BPA on hippocampal neurotransmission and its associated cognitive deficits. In addition, the histopathological examination with immunohistochemical detection of caspase-3 and NF-kB/p65 emphasized that EGCG failed to protect hippocampal CA3 neurons from apoptotic and necrotic effects induced by BPA. Our study revealed that EGCG showed no protective role against the neurotoxic effect caused by BPA, which may be attributed to its failure to counteract the BPA-induced oxidative stress in vivo. The controversial effect is probably related to EGCG’s ability to impede BPA glucuronidation and thus, its detoxification. That inference requires further additional experimental and clinical studies. Graphical abstract

Gamma radiation preparation of chitosan nanoparticles for controlled delivery of memantine

2019 ◽  
Vol 34 (8) ◽  
pp. 1150-1162 ◽  
Author(s):  
Rasha R Radwan ◽  
Ashraf M Abdel Ghaffar ◽  
Hussein E Ali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gamma Radiation ◽  
Histopathological Examination ◽  
Chitosan Nanoparticles ◽  
Amyloid Β ◽  
Brain Targeting ◽  
Morris Water Maze Test ◽  
Infrared Analysis ◽  
Amyloid Β Peptide

The purpose of the current study is to prepare chitosan nanoparticles by gamma radiation as a new brain delivery system for memantine to improve its therapeutic efficiency. Fourier-transform infrared analysis of chitosan nanoparticles showed the characteristic peaks of chitosan and the reduction of particle size induced by irradiation at doses 10, 20 and 30 kGy. The solubility of chitosan nanoparticles was tested using different solvents and exhibited good solubility in both water and 1% acetic acid than other tested solvents at 80°C. Different formulations containing memantine -loaded chitosan nanoparticles were evaluated for brain targeting on aluminum-induced Alzheimer’s disease in rats. Memory deficit was evaluated using the Morris water maze test. The levels of amyloid-β peptide, tumour necrosis factor alpha, interleukin-1β and interleukin-6 in brain tissues as well as the serum level of brain-derived neurotrophic factor were assayed. Data demonstrated that memantine -loaded chitosan nanoparticles 1:1 transported memantine effectively into the brain compared to free memantine as evidenced by better behaviour performance and biochemical amelioration and confirmed by histopathological examination in Alzheimer’s disease rats. Interestingly, the therapeutic effect of memantine -loaded chitosan nanoparticles 1:1 was superior to memantine -loaded chitosan nanoparticles 1:2 and memantine -loaded chitosan nanoparticles 2:1. Based on these findings, it is reasonable to suggest that memantine -loaded chitosan nanoparticles 1:1 could be a promising approach for Alzheimer’s disease.

scholarly journals Enteromorpha prolifera Extract Improves Memory in Scopolamine-Treated Mice via Downregulating Amyloid-β Expression and Upregulating BDNF/TrkB Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 620
Author(s):  
Seung Yeon Baek ◽  
Fu Yi Li ◽  
Da Hee Kim ◽  
Su Jin Kim ◽  
Mee Ree Kim
Keyword(s):  
Oxidative Stress ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Morris Water Maze Test ◽  
Marker Enzyme ◽  
Enteromorpha Prolifera ◽  
Memory Impairments ◽  
Traditional Remedies ◽  
Preliminary Study ◽  
The Brain

Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or water extracts. Nonetheless, there has been no report on the effect of EAEP on memory impairment due to oxidative damage. This study investigated whether EAEP could attenuate memory deficits in an oxidative stress-induced mouse model. EAEP was orally administered (50 or 100 mg/kg body weight (b.w.)) to mice and then scopolamine was administered. The oral administration of EAEP at 100 mg/kg b.w. significantly restored memory impairments induced by scopolamine, as evaluated by the Morris water maze test, and the passive avoidance test. Further, EAEP upregulated the protein expression of BDNF, p-CREB, p-TrkB, and p-Akt. Moreover, EAEP downregulated the expression of amyloid-β, tau, and APP. The regulation of cholinergic marker enzyme activities and the protection of neuronal cells from oxidative stress-induced cell death in the brain of mice via the downregulation of amyloid-β and the upregulation of the BDNF/TrkB pathway by EAEP suggest its potential as a pharmaceutical candidate to prevent neurodegenerative diseases.

Effect of barley grain on memory and brain’s oxidative stress factors in male rats

2020 ◽  
Vol 10 ◽  
Author(s):  
Batool Shakiba ◽  
Azam Moghani ◽  
Marzieh Kafami ◽  
Mahmoud Hosseini ◽  
Masoud Hosseinzadeh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Feed ◽  
Memory Function ◽  
Barley Grain ◽  
Stress Factors ◽  
Male Rats ◽  
Barley Seed ◽  
Saline Control ◽  
Albino Rats ◽  
Protective Effects

Background & Objective: Barley is widely used as a major staple of human food and animal feed. Several antioxidant phenols are found in barely, which have scavenging properties. The present study aimed to assess the protective effects of barley seed against the oxidative damage of brain tissues in a scopolamine-induced memory impairment model. Materials and Methods: In total, 32 male albino rats (mean weight: 250±10 g) were divided into four groups of saline (control), scopolamine, barley seed (100 mg/kg) with scopolamine, and barley seed alone. The spatial memory function was assessed using the Morris water maze. Results: Compared to the scopolamine group, barley seed could decrease the escape latency time in the treated rats, while the time spent and distance traveled in the target quadrant on the probe trial increased. Moreover, barley seed could increase the malondialdehyde concentration in the hippocampus and cortical tissues, while the thiol content was observed to decrease. Conclusion: According to the results, the use of dietary barley seed could improve the memory function in dementia associated with increased oxidative stress.

Anti-ulcerogenic effect of the methanol extract of Chasmanthera dependens (Hochst) stem on male Wistar rats

2018 ◽  
Vol 29 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Stephanie Abiola Tijani ◽  
Samuel B. Olaleye ◽  
Ebenezer O. Farombi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Gastric Ulcer ◽  
Gastric Mucosa ◽  
Antioxidant System ◽  
Methanol Extract ◽  
Histopathological Examination ◽  
Antioxidant Properties ◽  
Male Rats ◽  
Standard Drug

AbstractBackgroundOxidative stress and free radical-mediated processes have been implicated in the pathogenesis of indomethacin-induced gastric ulcer. This study investigated the ability of the methanol extract ofChasmanthera dependensto protect the gastric mucosal from oxidative damage induced by oral administration of indomethacin in rats.MethodsTheC. dependensstems were chopped into pieces, air-dried, and pulverized into powder. One kilogram of the powder was macerated in 1 L of methanol for 72 h. The mixture was filtered and evaporated using rotatory evaporator to obtain the extract ofC. dependens. Adult male rats were divided into eight groups of six animals per group and were pretreated orally with the methanol extract ofC. dependens(200, 400, and 800 mg/kg) or cimetidine (CIM), a standard drug (50 mg/kg), for 7 days. Gastric ulcer was induced orally with indomethacin. Ulcerogenic parameters, oxidative stress indices, and histopathological examination of the stomach were assessed to monitor the gastroprotective potential ofC. dependensstem.ResultsIndomethacin caused severe gastric mucosa damage and significant reduction in the gastric mucosa antioxidant system with concomitant increase in the level of lipid peroxidation. Pretreatment with the methanol extract ofC. dependensor CIM significantly reduced the formation of ulcer at the different doses administered. Similarly, pretreatments with the extract or CIM improved the antioxidant system, decreased acid output, lipid peroxidation, and improved the architecture of the gastric mucosa in ulcerated rats.ConclusionsThe results show the gastroprotective effect of the methanolic extract ofC. dependens, which may be attributed to its antioxidant properties.

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