scholarly journals Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) and Modulating Inflammation on the Gut-brain Axis

2020 ◽  
Author(s):  
Zeping Xie ◽  
Hui Lu ◽  
Sixia Yang ◽  
Yi Zeng ◽  
Wei Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Therapeutic Effect ◽  
Memory Loss ◽  
Field Tests ◽  
Beta Amyloid ◽  
Illumina Miseq ◽  
Peripheral Circulation ◽  
Neuroprotective Effects ◽  
Multiplex Immunoassay ◽  
Significant Difference

Abstract Background Alzheimer’s disease (AD), as the most prime cause of dementia, is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, A range of therapeutic approaches have shown unsatisfactory outcomes in clinical setting. Thus, it is critical to develop alternative therapies for the treatment of AD. Salidroside(SAL), a herb-derived phenylpropanoid glycoside compound, has been shown to attenuate LPS-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here we show a therapeutic effect of SAL in a reliable and stable mouse model of AD, Senescence-Accelerated Mice Prone 8 (SAMP8).Methods SAMP8 were treated with salidroside, donepezil or saline, cognitive behavioral impairments were assessed using the Morris water maze, Y-maze, and open-field tests. Fecal samples were collected and analyzed by 16S rRNA sequencing, performed on the Illumina MiSEq. Brain samples were analyzed by immunohistochemistry and western blot to detect Beta Amyloid 1–42 deposition. Activation in microglia and neuroinflammatory cytokines was detected by immunofluorescence, Western blot and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel and performed on the Luminex-MAGPIX multiplex immunoassay system.Results Our results suggested that SAL effectively alleviated hippocampus-dependent memory impairment in SAMP8, and showed no significant difference compared with the donepezil-administration group. SAL significantly (1) reduced toxic beta-amyloid (Abeta) 1–42 deposition; (2) reduced activation of microglia and attenuated proinflammatory factors, IL-1β, IL-6, and TNF-α, in the brain; (3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes, and eliminated Clostridiales and Streptococcaceae, which may have been associated with cognitive deficits); and (4) decreased the levels of proinflammatory cytokines in the peripheral circulation, IL-1α, IL-6, IL-17A and IL-12 in particular, according to a multiplex immunoassay.Conclusion In summary, SAL reversed AD-related changes in SAMP8 potentially through the regulation of the microbiota-gut-brain axis and by modulating inflammation in both peripheral circulation and central nervous system. Our results strongly suggest a therapeutic effect of SAL on cognition-related changes in SAMP8 and highlight its value as a potential source for drug development.

scholarly journals Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice and Modulates Inflammation of the Gut-Brain Axis

2020 ◽  
Vol 11 ◽  
Author(s):  
Zeping Xie ◽  
Hui Lu ◽  
Sixia Yang ◽  
Yi Zeng ◽  
Wei Li ◽  
...  
Keyword(s):  
Western Blotting ◽  
Memory Loss ◽  
High Sensitivity ◽  
Illumina Miseq ◽  
Magnetic Bead ◽  
Peripheral Circulation ◽  
Neuroprotective Effects ◽  
Multiplex Immunoassay ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

Background: Alzheimer’s disease (AD) is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, several therapeutic approaches have shown unsatisfactory outcomes in the clinical setting. Thus, developing alternative therapies for the prevention and treatment of AD is critical. Salidroside (SAL) is critical, an herb-derived phenylpropanoid glycoside compound, has been shown to attenuate lipopolysaccharide (LPS)-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here, we show that SAL has a therapeutic effect in the senescence-accelerated mouse prone 8 (SAMP8) strain, a reliable and stable mouse model of AD.Methods: SAMP8 mice were treated with SAL, donepezil (DNP) or saline, and cognitive behavioral impairments were assessed using the Morris water maze (MWM), Y maze, and open field test (OFT). Fecal samples were collected and analyzed by 16S rRNA sequencing on an Illumina MiSeq system. Brain samples were analyzed to detect beta-amyloid (Aβ) 1–42 (Aβ1-42) deposition by immunohistochemistry (IHC) and western blotting. The activation of microglia and neuroinflammatory cytokines was detected by immunofluorescence (IF), western blotting and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel on a Luminex-MAGPIX multiplex immunoassay system.Results: Our results suggest that SAL effectively alleviated hippocampus-dependent memory impairment in the SAMP8 mice. SAL significantly 1) reduced toxic Aβ1-42 deposition; 2) reduced microglial activation and attenuated the levels of the proinflammatory factors IL-1β, IL-6, and TNF-α in the brain; 3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes and eliminated Clostridiales and Streptococcaceae, which may be associated with cognitive deficits); and 4) decreased the levels of proinflammatory cytokines, particularly IL-1α, IL-6, IL-17A and IL-12, in the peripheral circulation, as determined by a multiplex immunoassay.Conclusion: In summary, SAL reversed AD-related changes in SAMP8 mice, potentially by regulating the microbiota-gut-brain axis and modulating inflammation in both the peripheral circulation and central nervous system. Our results strongly suggest that SAL has a preventive effect on cognition-related changes in SAMP8 mice and highlight its value as a potential agent for drug development.

The neuroprotective effects of flupirtine and beta-amyloid induced memory impairment

2011 ◽  
Author(s):  
Matthew Jefferson ◽  
Sara Smeltzer ◽  
Jeffery L. McMillin ◽  
Caitlin C. Henry ◽  
Brittney M. Klauser ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Beta Amyloid ◽  
Neuroprotective Effects

Role of MicroRNA Genes miR-1000 and miR-375 in Forming Olfactory Conditional Memory in Drosophila melanogaster

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Sadniman Rahman ◽  
Chaity Modak ◽  
Mousumi Akter ◽  
Mohammad Shamimul Alam
Keyword(s):  
Learning And Memory ◽  
Short Term Memory ◽  
Memory Loss ◽  
Memory Formation ◽  
Neural Integration ◽  
Significant Difference ◽  
Locomotion Speed ◽  
Microrna Genes ◽  
With Memory

Background: Learning and memory is basic aspects in neurogenetics as most of the neurological disorders start with dementia or memory loss. Several genes associated with memory formation have been discovered. MicroRNA genes miR-1000 and miR-375 were reported to be associated with neural integration and glucose homeostasis in some insects and vertebrates. However, neuronal function of these genes is yet to be established in D. melanogaster. Objective: Possible role of miR-1000 and miR-375 in learning and memory formation in this fly has been explored in the present study. Methods: Both appetitive and aversive olfactory conditional learning were tested in the miR-1000 and miR-375 knockout (KO) strains and compared with wild one. Five days old third instar larvae were trained by allowing them to be associated with an odor with reward (fructose) or punishment (salt). Then, the larvae were tested to calculate their preferences to the odor trained with. Learning index (LI) values and larval locomotion speed were calculated for all strains. Results: No significant difference was observed for larval locomotion speed in mutant strains. Knockout strain of miR-1000 showed significant deficiency in both appetitive and aversive memory formation whereas miR-375 KO strain showed a significantly lower response only in appetitive one. Conclusion: The results of the present study indicate important role played by these two genes in forming short-term memory in D. melanogaster.

scholarly journals The Alterations in Methylene Blue/Light-Treated Frozen Plasma Proteins Revealed by Proteomics

2021 ◽  
pp. 1-8
Author(s):  
Tiange Wu ◽  
Xiaoning Wang ◽  
Kai Ren ◽  
Xiaochen Huang ◽  
Jiankai Liu
Keyword(s):  
Mass Spectrometry ◽  
Methylene Blue ◽  
Western Blot ◽  
Blue Light ◽  
Differentially Expressed ◽  
Enzyme Linked Immunosorbent Assay ◽  
Differentially Expressed Protein ◽  
Significant Difference ◽  
Modified Proteins ◽  
Frozen Plasma

Introduction: The aim of this study was to investigate the modified proteins in methylene blue/light-treated frozen plasma (MB-FP) compared with fresh frozen plasma (FFP) in order to gain a better application of MB/light-treated plasma in clinic transfusion. Methods: MB-FP and FFP were collected from Changchun central blood station, and a trichloroacetic acid/acetone precipitation method was used to remove albumin for the enrichment of lower abundance proteins. The plasma protein in MB-FP and FFP were separated using two-dimensional gel electrophoresis (2-DE) and the differentially expressed protein spots were analyzed using mass spectrometry. Finally, the differentially expressed proteins were tested using Western blot and enzyme-linked immunosorbent assay (ELISA). Results: Approximately 14 differentially expressed protein spots were detected in the MB-FP, and FFP was chosen as the control. After 2-DE comparison analysis and mass spectrometry, 8 significantly differentially expressed protein spots were identified, corresponding to 6 different proteins, including complement C1r subcomponent (C1R), inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4), keratin, type II cytoskeletal 1 (KRT1), hemopexin (HPX), fibrinogen gamma chain (FGG), and transthyretin (TTR). Western blot showed no significant difference in the expression level of KRT1 between MB-FP and FFP (p > 0.05). Both Western blot and ELISA indicated that the level of HPX was significantly higher in FFP than in MB-FP (p < 0.05). Conclusion: This comparative proteomics study revealed that some significantly modified proteins occur in MB-FP, such as C1R, ITI-H4, KRT1, HPX, FGG, and TTR. Our findings provide more theoretical data for using MB-FP in transfusion medicine. However, the relevance of the data for the transfusion of methylene blue/light-treated plasma remains unclear. The exact modification of these proteins and the effects of these modified proteins on their functions and their effects in clinical plasma infusion need to be further studied.

scholarly journals CD36 deficiency ameliorates drug-induced acute liver injury in mice

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Chen Zhang ◽  
Xiao Shi ◽  
Zhongping Su ◽  
Chao Hu ◽  
Xianmin Mu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Western Blot ◽  
Kinase Inhibitor ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Protein Adducts ◽  
Sterile Inflammation ◽  
Inflammatory Factor ◽  
Cd36 Deficiency ◽  
Significant Difference

Abstract Background Acetaminophen (APAP) overdose causes hepatotoxicity and even acute liver failure. Recent studies indicate that sterile inflammation and innate immune cells may play important roles in damage-induced hepatocytes regeneration and liver repair. The scavenger receptor CD36 has its crucial functions in sterile inflammation. However, the roles of CD36 in APAP induced acute liver injury remain unclear and warrant further investigation. Methods WT C57BL/6 J and CD36−/− mice were intraperitoneally injected with APAP (300 mg/kg) after fasting for 16 h. Liver injury was evaluated by serum alanine aminotransferase (ALT) level and liver tissue hematoxylin and eosin (H&E) staining. Liver inflammatory factor expression was determined by real-time polymerase chain reaction (PCR). The protein adducts forming from the metabolite of APAP and the metabolism enzyme cytochrome P450 2E1 (CYP2E1) levels were measured by Western blot. Liver infiltrating macrophages and neutrophils were characterized by flow cytometry. RNA sequencing and Western blot were used to evaluate the effect of damage-associated molecular patterns (DAMP) molecule high mobility group B1 (HMGB1) on WT and CD36−/− macrophages. Moreover, PP2, a Src kinase inhibitor, blocking CD36 signaling, was applied in APAP model. Results The expression of CD36 was increased in the liver of mice after APAP treatment. Compared with WT mice, APAP treated CD36−/− mice show less liver injury. There was no significant difference in APAP protein adducts and CYP2E1 expression between these two strains. However, reduced pro-inflammatory factor mRNA expression and serum IL-1β level were observed in APAP treated CD36−/− mice as well as infiltrating macrophages and neutrophils. Moreover, CD36 deficiency impaired the activation of c-Jun N-terminal kinase (JNK) caused by APAP. Interestingly, the lack of CD36 reduced the activation of extracellular regulated protein kinases (Erk) and v-akt murine thymoma viral oncogene homolog (Akt) induced by HMGB1. RNA transcription sequencing data indicated that HMGB1 has a different effect on WT and CD36−/− macrophages. Furthermore, treatment with PP2 attenuated APAP induced mouse liver injury. Conclusion Our data demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.

scholarly journals The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James M. Brimson ◽  
Sirikalaya Brimson ◽  
Mani Iyer Prasanth ◽  
Premrutai Thitilertdecha ◽  
Dicson Sheeja Malar ◽  
...  
Keyword(s):  
Plant Extracts ◽  
Neurological Diseases ◽  
Digit Span ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Memory Loss ◽  
Learning Task ◽  
Inspection Time ◽  
Neuroprotective Effects

AbstractBacopamonnieri (Linn.) Wettst. has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B. monnieri's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and ‘n’ numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B. monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B. monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer’s disease, and depression which cannot be solely credited as the effect of B. monnieri. Although in one study B. monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B. monnieri. More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.

Neuroprotective effects of sigma-1 receptor agonists against beta-amyloid-induced toxicity

Neuroreport ◽  
2005 ◽  
Vol 16 (11) ◽  
pp. 1223-1226 ◽  
Author(s):  
Agostino Marrazzo ◽  
Filippo Caraci ◽  
Elisa Trovato Salinaro ◽  
Tsung-Ping Su ◽  
Agata Copani ◽  
...  
Keyword(s):  
Beta Amyloid ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
Receptor Agonists ◽  
Sigma 1

Abstract TMP3: Low Concentration Normobaric Oxygen Enhanced Therapeutic Effect of Mild Hypothermia or Ethanol Through a Reduction in Apoptosis

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kaiyin Liu ◽  
Lipeng Cai ◽  
Changya Peng ◽  
Xiaokun Geng ◽  
Xunming Ji ◽  
...  
Keyword(s):  
Cell Death ◽  
Therapeutic Effect ◽  
Mild Hypothermia ◽  
Apoptotic Cell ◽  
Artery Occlusion ◽  
Apoptotic Cell Death ◽  
Tissue Type ◽  
Neuroprotective Effects ◽  
Normobaric Oxygen ◽  
Low Concentration

Introduction: Neuroprotective effects of normobaric oxygen (NBO) and ethanol (EtOH) has been shown. In a clinically relevant autologous embolus rat stroke model in which reperfusion was established by tissue-type plasminogen activator (rt-PA), the present study further evaluated whether low concentration NBO enhanced therapeutic effect of mild hypothermia (Hypo) or EtOH through a reduction in apoptosis and whether EtOH can substitute for hypothermia. Hypothesis: Hypo and EtOH has been shown to have neuroprotective effects through similar mechanisms. We assessed the hypothesis that low concentration NBO, whose neuroprotective effects are currently debated, has benefit in our stroke models, and we further assessed the hypothesis that EtOH can substitute for Hypo in the presence of tPA and NBO. Methods: At 1 hour of middle cerebral artery occlusion (MCAO) by an autologous embolus, rats (96 total, 12 in each treatment group) received rt-PA and other treatments of either EtOH (1.0 g/kg) or Hypo (33 °C for 3 hours) in combination with NBO (60% for 3 hours). Apoptotic cell death was measured by ELISA. Western immunoblotting was performed for pro- (AIF, Caspase-3, Bax) and anti-apoptotic (Bcl-2) protein expression at 3 and 24 hours of reperfusion. Results: Compared to ischemic rats treated only with rt-PA, animals with NBO, hypothermia or EtOH had significantly reduced apoptotic cell death by 32.5%, 43.1% and 36.0% respectively. However, combination therapy that included NBO+EtOH or NBO+Hypo with rt-PA exhibited a much larger decline (p<0.01) in the cell death by 71.1% and 73.6%, respectively. Similarly, NBO+EtOH or NBO+Hypo treatment in addition to rt-PA enhanced beneficial effects on both pro- and anti-apoptotic protein expressions as compared to other options. Conclusions: Neuroprotection after reperfusion with rt-PA in ischemic stroke induced by thromboembolism are enhanced by combination treatment with either EtOH or Hypo in the presence of 60% NBO through reduced apoptosis. Since the effects produced by EtOH and Hypo are comparable, their mechanism of action may not only be similar but also could be interchangeable. Since EtOH administration does not lead to temperature decrease, EtOH may a better alternative than Hypo.

Effect of feeding with bilberry fruit on the expression pattern of αCaMKII in hippocampal neurons in normal and diabetic rats

2017 ◽  
Vol 20 (2) ◽  
pp. 313-319 ◽  
Author(s):  
M. Matysek ◽  
S. Mozel ◽  
R. Szalak ◽  
A. Zacharko-Siembida ◽  
K. Obszańska ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Hippocampal Neurons ◽  
Negative Impact ◽  
Expression Patterns ◽  
Memory Loss ◽  
Diabetic Rats ◽  
Control Group ◽  
Neuroprotective Effects ◽  
The Central Nervous System ◽  
And Control

Abstract αCaMKII, widely occurring in the central nervous system, plays a significant role in cognitive processes. It is well known that diabetes is a risk factor that may trigger brain atrophy, cognitive dysfunction and finally lead to memory loss. Antioxidants richly present in bilberry fruits are believed to have significant effects on diabetes-related brain dysfunctions mainly due to their abilities to modulate neurotransmitter release that lead to reduction of the negative impact of free radicals on cognitive processes. The aim of the present research was to immunohistochemically investigate the expression patterns of αCaMKII in hippocampal neurons from non-diabetic, diabetic and diabetic rats fed with an extract of bilberry fruit. The obtained results show that in comparison to the control group, in diabetic rats hippocampal neurons immunoreactive (ir) to αCaMKII were swollen and the lengths of the neuronal fibres were reduced. Further study shows that in diabetic rats fed with bilberry fruit, αCaMKII-positive nerve fibres were significantly longer when compared to the groups of diabetic and control rats. Additionally, we observed statistically significant changes in the average larger diameter of αCaMKII-ir hippocampal neurons between groups of diabetic rats (with vs. without supplement of bilberry fruit). The results of the present work suggest that antioxidants present in bilberry fruits influence the morphology of and possibly exhibit beneficial and neuroprotective effects on hippocampal neurons during diabetes. It is likely that changes in the appearance of αCaMKII-expressed hippocampal neurons may reflect the diabetes-evoked rise in Ca2+ level in the cerebral nerve terminals. The present research extends our knowledge of preventive mechanisms for cognitive dysfunctions occurring in the brain during diabetes.

scholarly journals Inhibitory and complementary therapeutic effect of sweet lime (Citrus limetta) against RNA-viruses

2021 ◽  
Vol 7 (1) ◽  
pp. 37-44
Author(s):  
Sulagna Ray Pal ◽  
Swapan Banerjee
Keyword(s):  
Therapeutic Effect ◽  
Rna Viruses ◽  
Current Knowledge ◽  
Western World ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Nutrient Contents ◽  
Therapeutic Benefits ◽  
Sweet Lime ◽  
Antiviral Activities

Sweet lime (), known as 'Mousambi' or 'Mosambi' in India, is one of the best citrus fruits regarding its nutrient contents. Its bioactive compounds (BAC) are exclusively used for multiple clinical applications considering many therapeutic benefits not only in Asian countries but also in the western world. The fruit pulp and juice are the best sources of ascorbic acid, B-vitamins, amino acids, and other secondary metabolites. Specifically, polyphenols such as flavanones, hesperetin, naringenin, and chlorogenic acid are highly rich in the fruit. The nutrients in sweet lime altogether provide significant anti-inflammatory, antioxidant, anti-cancer, and neuroprotective effects. The purpose of this study is to review and analyze the inhibitory and complementary therapeutic effects of sweet lime's pulp and juices to inhibit the virulence caused by RNA viruses, mainly SARS-CoV-2. This review study was designed based on extensive online searches of relevant open-access literature available in the best quality and reliable databases by using specific keywords and boolean operators. After a rigorous review, we found that flavanones in the fruit can alter or inhibit the polyproteins (pp1a and pp1b) responsible for viral replication. Therefore, sweet lime has potentialities to provide an inhibitory and a complementary therapeutic effect against RNA viruses, mainly SARS-CoV-2. About the antiviral activities, more clinical trials are needed to prove its efficacy; however, reviewing current knowledge, is one of the potent antioxidant, inflammatory fruits available and affordable almost worldwide.

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