scholarly journals In vitro anti-cholinesterase activity and in vivo screening of Coccoloba uvifera, Mimusops elengi and Syzygium aqueum extracts on learning and memory function of chronic cerebral hypoperfusion rat

2021 ◽  
Vol 4 (2) ◽  
pp. 1-13
Author(s):  
Kesevan Rajah Kumaran ◽  
Habibah Abdul Wahab ◽  
Zurina Hassan
Keyword(s):  
Learning And Memory ◽  
Plant Extracts ◽  
Cholinesterase Activity ◽  
Memory Function ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ageing Population ◽  
Mimusops Elengi

Vascular dementia (VaD), is one of the most common types of dementia in the ageing population, initiated by chronic cerebral hypoperfusion (CCH). At present, effective therapeutic approaches to cure VaD are still missing. Cholinergic system dysfunction in the central nervous system (CNS) has been recognised as one of the main reasons for learning and memory impairment in VaD patients. Therefore, medications that restore the level of acetylcholine (ACh) neurotransmitter by inhibiting cholinesterase activity were proposed as a potential candidate to treat VaD patients. Permanent occlusion of bilateral common carotid arteries (POBCCA) surgery method was performed to develop CCH model in rats. The present study evaluated the anti-cholinesterase activity of three Malaysian plant methanol leaf extracts in vitro and further validated its cognitive-enhancing effects in vivo using POBCCA rats. The selected plant extracts were Coccoloba uvifera (stems), Mimusops elengi (leaves) and Syzygium aqueum (leaves). The in vitro anti-cholinesterase activities of these plants were determined using Ellman's method. The effects of selected plant extracts (100 and 200 mg/kg, p.o.) on learning and memory functions were evaluated using a series of behavioural tests. All the selected plant extracts exhibited good anti-acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in vitro, with IC50 ranging from 3.67 to 16.04 and 5.6 to 13.95 µg/mL, respectively. Extracts of S. aqueum (200 mg/kg) improve both short- and long-term recognition memories, whereas M. elengi and S. aqueum (200 mg/kg) extracts improve spatial learning. None of the extracts impaired motor and exploratory functions in POBCCA rats. In conclusion, methanol extracts of C. uvifera, M. elengi and S. aqueum showed good anti-cholinesterase activity in vitro. However, only M. elengi and S. aqueum improve learning and memory function in POBCCA rats.

scholarly journals Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

2015 ◽  
Vol 35 (9) ◽  
pp. 1435-1444 ◽  
Author(s):  
Tingting Dong ◽  
Qi Zhang ◽  
Michael R Hamblin ◽  
Mei X Wu
Keyword(s):  
Learning And Memory ◽  
Memory Function ◽  
Light Illumination ◽  
Low Level ◽  
Metabolic Substrates ◽  
Secondary Damage ◽  
Injured Brain ◽  
Combinational Treatment

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue–like injured brain.

scholarly journals Curcumin Protects Against Cognitive Impairments in a Rat Model of Chronic Cerebral Hypoperfusion Combined with Diabetes Mellitus by Suppressing Neuroinflammation, Apoptosis, and Pyroptosis

2020 ◽  
Author(s):  
Yaling Zheng ◽  
Jiawei Zhang ◽  
Yao Zhao ◽  
Yaxuan Zhang ◽  
Xiaojie Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairments ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Receptor Protein ◽  
Therapeutic Effects ◽  
Protective Effects

Abstract BackgroundChronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline in vascular dementia (VaD). We have previously shown that diabetes mellitus (DM) synergistically promotes CCH-induced cognitive dysfunction via exacerbating neuroinflammation. Furthermore, curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. However, the effects of curcumin on CCH-induced cognitive impairments in DM have remained unknown.MethodsRats were fed with a high-fat diet (HFD) and injected with low-dose streptozotocin (STZ), followed by bilateral common carotid artery occlusion (BCCAO), to model DM and CCH in vivo. After BCCAO, curcumin (50 mg/kg) was administered intraperitoneally every two days for eight weeks to evaluate its therapeutic effects. Additionally, mouse BV2 microglial cells were exposed to hypoxia and high glucose to model CCH and DM pathologies in vitro. ResultsCurcumin treatment significantly improved DM/CCH-induced cognitive deficits and attenuated neuronal cell death. Molecular analysis revealed that curcumin exerted protective effects via suppressing neuroinflammation induced by microglial activation, regulating the triggering receptor expressed on myeloid cells 2 (TREM2)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, alleviating apoptosis, and reducing nod-like receptor protein 3 (NLRP3)-dependent pyroptosis.ConclusionsTaken together, our findings suggest that curcumin represents a promising therapy for DM/CCH-induced cognitive impairments.

scholarly journals NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yao Zhao ◽  
Jiawei Zhang ◽  
Yaling Zheng ◽  
Yaxuan Zhang ◽  
Xiao Jie Zhang ◽  
...  
Keyword(s):  
Mitochondrial Damage ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ros Production ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Mechanistic Pathway ◽  
Bv2 Microglia

Abstract Background Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating neuroinflammation has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD+) shows anti-inflammatory and anti-oxidant effects in many neurodegenerative disease models, but its role in the chronic cerebral hypoperfusion (CCH) is still unclear. Methods The bilateral common carotid artery occlusion (BCCAO) was performed to establish CCH models in Sprague-Dawley rats. The rats were given daily intraperitoneal injection of NAD+ for 8 weeks. The behavioral test and markers for neuronal death and neuroinflammation were analyzed. Mitochondrial damage and ROS production in microglia were also assessed. RNA-seq was performed to investigate the mechanistic pathway changes. For in vitro studies, Sirt1 was overexpressed in BV2 microglial cells to compare with NAD+ treatment effects on mitochondrial injury and neuroinflammation. Results NAD+ administration rescued cognitive deficits and inhibited neuroinflammation by protecting mitochondria and decreasing ROS production in CCH rats. Results of mechanistic pathway analysis indicated that the detrimental effects of CCH might be associated with decreased gene expression of PPAR-γ co-activator1α (PGC-1α) and its upstream transcription factor Sirt1, while NAD+ treatment markedly reversed their decrease. In vitro study confirmed that NAD+ administration had protective effects on hypoxia-induced neuroinflammation and mitochondrial damage, as well as ROS production in BV2 microglia via Sirt1/PGC-1α pathway. Sirt1 overexpression mimicked the protective effects of NAD+ treatment in BV2 microglia. Conclusions NAD+ ameliorated cognitive impairment and dampened neuroinflammation in CCH models in vivo and in vitro, and these beneficial effects were associated with mitochondrial protection and ROS inhibition via activating Sirt1/PGC-1α pathway.

Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation

2021 ◽  
pp. 1-11
Author(s):  
Yanhu Ge ◽  
Duomao Lin ◽  
Boqun Cui ◽  
Liang Zhang ◽  
Shurong Li ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Noncoding Rna ◽  
Memory Function ◽  
Morris Water Maze Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spatial Learning And Memory ◽  
Target Area ◽  
Ht22 Cells

<b><i>Introduction:</i></b> Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified. <b><i>Methods:</i></b> ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay. <b><i>Results:</i></b> 1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19. <b><i>Conclusion:</i></b> Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.

scholarly journals The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both In Vivo and In Vitro Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of Aβ and Autophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Yan Liu ◽  
Xiaobo Huang ◽  
Wenqiang Chen ◽  
Yujing Chen ◽  
Ningqun Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Hippocampal Neurons ◽  
The Elderly ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Dependent Manner ◽  
Active Ingredients ◽  
Related Proteins

Chronic cerebral hypoperfusion (CCH) is closely related to the occurrence of Alzheimer’s disease (AD) in the elderly. CCH can induce overactivation of autophagy, which increases the deposition of amyloid-β (Aβ) plaques in the brain, eventually impairing the cognitive function. Yuan-Zhi decoction (YZD) is a traditional Chinese medicine (TCM) formulation that is used to treat cognitive dysfunction in the elderly, but the specific mechanism is still unclear. In this study, we simulated CCH in a rat model through bilateral common carotid artery occlusion (BCCAO) and treated the animals with YZD. Standard neurological tests indicated that YZD significantly restored the impaired cognitive function after BCCAO in a dose-dependent manner. Furthermore, YZD also decreased the levels of Aβ aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An in vitro model of CCH was also established by exposing primary rat hippocampal neurons to hypoxia and hypoglycemia (H-H). YZD and its active ingredients increased the survival of these neurons and decreased the levels of Aβ1-40 and Aβ1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both Aβ aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets Aβ, autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.

scholarly journals TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiawei Zhang ◽  
Yu Liu ◽  
Yaling Zheng ◽  
Yan Luo ◽  
Yu Du ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
High Glucose ◽  
Mapk Signaling ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

Abstract Background Diabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown. Methods To investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively. Results Cognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent pro-inflammatory mediator production under high glucose and hypoxia condition. Conclusions These results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.

scholarly journals NAD+ Improves Cognitive Function and Reduces Neuroinflammation By Ameliorating Mitochondrial Damage and Decreasing ROS Production in Chronic Cerebral Hypoperfusion Models Through Sirt1/PGC-1α Pathway

2021 ◽  
Author(s):  
Yao Zhao ◽  
Jiawei Zhang ◽  
Yaling Zheng ◽  
Yaxuan Zhang ◽  
Xiaojie Zhang ◽  
...  
Keyword(s):  
Mitochondrial Damage ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ros Production ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Mechanistic Pathway ◽  
Bv2 Microglia

Abstract Background: Microglial mediated neuroinflammation plays an important role in vascular dementia, and modulating neuroinflammation has emerged as a promising treatment target. NAD + shows anti-inflammatory and anti-oxidant effects in many neurodegenerative disease models, but its role in the chronic cerebral hypoperfusion (CCH) is still unclear. Methods: The bilateral common carotid artery occlusion (BCCAO) was performed to establish CCH models in Sprague-Dawley rats. The rats were given daily intraperitoneal injection of NAD + for 8 weeks. Behavioral test and markers for neuronal death and neuroinflammation were analyzed. Mitochondrial damage and ROS production in microglia were also assessed. RNA-seq was performed to investigate the mechanistic pathway changes. For in vitro studies, Sirt1 was overexpressed in BV2 microglial cells to compare with NAD + treatment effects on mitochondrial injury and neuroinflammation. Results: NAD + administration rescued cognitive deficits and inhibited neuroinflammation by protecting mitochondria and decreasing ROS production in CCH rats. Results of mechanistic pathway analysis indicated that the detrimental effects of CCH might be associated with decreased gene expression of PPAR-γ co-activator1α (PGC-1α) and its upstream transcription factor Sirt1 , while NAD + treatment markedly reversed their decrease. In vitro study confirmed that NAD + administration had protective effects on hypoxia induced neuroinflammation and mitochondrial damage, as well as ROS production in BV2 microglia via Sirt1/PGC-1α pathway. Sirt1 overexpression mimicked the protective effects of NAD + treatment in BV2 microglia.Conclusions: NAD + ameliorated cognitive impairment and dampened neuroinflammation in CCH models in vivo and vitro, and these beneficial effects were associated with mitochondrial protection and ROS inhibition via activating Sirt1/PGC-1α pathway. Keywords: Chronic cerebral hypoperfusion, microglia, NAD + , mitochondria, ROS

EPA-enriched ethanolamine plasmalogen and EPA-enriched phosphatidylethanolamine enhance BDNF/TrkB/CREB signaling and inhibit neuronal apoptosis in vitro and in vivo

2020 ◽  
Vol 11 (2) ◽  
pp. 1729-1739 ◽  
Author(s):  
Hongxia Che ◽  
Lingyu Zhang ◽  
Lin Ding ◽  
Wancui Xie ◽  
Xiaoming Jiang ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neuronal Apoptosis ◽  
Memory Deficit ◽  
Ethanolamine Plasmalogen ◽  
Learning And Memory Deficit

Our previous study showed that EPA-enriched ethanolamine plasmalogen (EPA-pPE) exerted more significant effects than EPA-enriched phosphatidylethanolamine (EPA-PE) in improving learning and memory deficit.

scholarly journals Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1503
Author(s):  
Carla Guijarro-Real ◽  
Mariola Plazas ◽  
Adrián Rodríguez-Burruezo ◽  
Jaime Prohens ◽  
Ana Fita
Keyword(s):  
Plant Extracts ◽  
Curcuma Longa ◽  
Hydrolysis Product ◽  
Resonance Energy ◽  
Significant Inhibition ◽  
Main Role ◽  
Turmeric Extract ◽  
Ic50 Value

Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CLPro) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CLPro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides) at 500 µg mL−1 displayed significant inhibition of the 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC50 value of 15.74 µg mL−1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibiting the 3CLPro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CLPro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC50 value of 41.43 µg mL−1. The current study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.

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