scholarly journals Amyloid Beta: Multiple Mechanisms of Toxicity and Only Some Protective Effects?

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Paul Carrillo-Mora ◽  
Rogelio Luna ◽  
Laura Colín-Barenque
Keyword(s):  
Amyloid Beta ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Experimental Conditions ◽  
Mechanisms Of Toxicity ◽  
Mitochondrial Alterations ◽  
Physiological Properties ◽  
Wide Range

Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer’s disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβin the pathophysiology of AD is not yet precisely understood. Aβhas been experimentally shown to have a wide range of toxic mechanismsin vivoandin vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβhas also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβmay depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβto further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

Exopolysaccharide from Bifidobacterium longum subsp. longum 35624™ modulates murine allergic airway responses

2018 ◽  
Vol 9 (5) ◽  
pp. 761-773 ◽  
Author(s):  
E. Schiavi ◽  
S. Plattner ◽  
N. Rodriguez-Perez ◽  
W. Barcik ◽  
R. Frei ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Bifidobacterium Longum ◽  
Immunological Tolerance ◽  
Respiratory Allergy ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Eosinophil Recruitment

Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B. longum 35624 cultures was used for in vitro, ex vivo and in vivo studies. Human monocyte-derived dendritic cells (MDDCs) were used to investigate in vitro immunological responses to EPS. Cytokine secretion, expression of surface markers and signalling pathways were examined. The ovalbumin (OVA) respiratory allergy murine model was used to evaluate the in vivo immunomodulatory potential of EPS. In addition, interleukin (IL)-10 knockout (KO) mice and anti-Toll-like receptor (TLR)-2 blocking antibody were used to examine the underlying protective mechanisms of intranasal EPS administration. Stimulation of human MDDCs with EPS resulted in IL-10 secretion, but not proinflammatory cytokines. IL-10 secretion was TLR-2-dependent. Eosinophil recruitment to the lungs was significantly decreased by EPS intranasal exposure, which was associated with decreased expression of the Th2-associated markers C-C motif chemokine 11 (CCL11), C-C chemokine receptor type 3 (CCR3), IL-4 and IL-13. TLR-2-mediated IL-10 secretion was shown to be required for the reduction in eosinophils and Th2 cytokines. EPS-treatment reduced eosinophil recruitment within the lung in a respiratory inflammation mouse model, which is both TLR-2 and IL-10 mediated. EPS can be considered as a novel molecule potentially reducing the severity of chronic eosinophil-related airway disorders.

scholarly journals ACE2/ANG-(1-7)/Mas Receptor Axis Activation Prevents Inflammation, Glial Activation And Cognitive Decline In a Rat Model of STZ Induced Impairment of Learning and Memory

2021 ◽  
Author(s):  
Virendra Tiwari ◽  
Jitendra Singh ◽  
Priya Tiwari ◽  
Swati Chaturvedi ◽  
Shivangi Gupta ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Rat Model ◽  
Protective Effects ◽  
Ang Ii ◽  
Diminazene Aceturate ◽  
Experimental Conditions ◽  
Mas Receptor ◽  
Amyloid Pathology

Abstract Activation of the renin-angiotensin system (RAS), mediated by Angiotensin converting enzyme/Angiotensin II/Angiotensin receptor-1 (ACE/Ang II/AT1 R) axis elicits amyloid pathology, induces neurodegeneration and cognitive impairment leading to Alzheimer's disease (AD). On the contrary, Angiotensin converting enzyme2 (ACE2) produces Ang -(1-7) which binds with the Mas receptor and counters ACE/Ang II/AT1 axis. To date, the involvement of ACE2/Ang-(1–7)/MasR axis in etiology and progression of AD largely remains to be elucidated. Hence, the present study is aimed to determine the role of ACE2/Ang-(1–7)/MasR axis in STZ induced model of neurodegeneration using Diminazene aceturate (DIZE), an ACE2 activator in both in vitro/in vivo experimental conditions. Interestingly, ROS content and oxidative stress burden in N2A cells were found to be attenuated along with a decrease in enzymatic activity of AChE following DIZE treatment. In contrast, activation of this axis led to altered mitochondrial membrane potential (MMP) in addition to ablated intracellular Ca2+ influx. ACE2/Ang-(1–7)/MasR axis activation further resulted in reduction of astrogliosis as indicated by decreased intensity of NFκB and dwindled expression of its downstream NLRP3 cascade signaling molecules. These results were confirmed by using a selective inhibitor of ACE-2, MLN-4760, which reversed the protective effects of ACE2 activation by DIZE. Subsequently, treatment with DIZE in STZ induced rat model of AD prevented cognitive impairment and progression of amyloid pathology. Therefore, the involvement of ACE2/Ang-(1–7)/Mas axis suggests that it could be further explored as a potential pathway in AD, owing to its inhibitory effect on inflammation/astrogliosis and restoring cognitive functions.

Protective Effects of Compounds from Cimicifuga dahurica against Amyloid Beta Production in Vitro and Scopolamine-Induced Memory Impairment in Vivo

2020 ◽  
Vol 83 (2) ◽  
pp. 223-230
Author(s):  
Sang-Bin Lee ◽  
Seo Young Yang ◽  
Nguyen Phuong Thao ◽  
Dae-Gun Seo ◽  
Sunggun Kim ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Memory Impairment ◽  
Protective Effects

Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo

2018 ◽  
Vol 15 (8) ◽  
pp. 731-742 ◽  
Author(s):  
José M. Cornejo-Montes-de-Oca ◽  
Rebeca Hernández-Soto ◽  
Arturo G. Isla ◽  
Carlos E. Morado-Urbina ◽  
Fernando Peña-Ortega
Keyword(s):  
Olfactory Bulb ◽  
Amyloid Beta ◽  
Amyloid Β ◽  
Tolfenamic Acid ◽  
Network Activity ◽  
Protective Effects ◽  
Population Activity ◽  
Activity Inhibition

Background: Amyloid beta inhibits olfactory bulb function. The mechanisms involved in this effect must include alterations in network excitability, inflammation and the activation of different transduction pathways. Thus, here we tested whether tolfenamic acid, a drug that modulates several of these pathological processes, could prevent amyloid beta-induced olfactory bulb dysfunction. Objective: To test whether tolfenamic acid prevents amyloid beta-induced alterations in olfactory bulb network function, olfaction and GSK3β activity. Method: The protective effects of tolfenamic acid against amyloid beta-induced population activity inhibition were tested in olfactory bulb slices from adult mice, while tolfenamic acid and amyloid beta were bath-applied. We also tested the effects of amyloid-beta in slices obtained from animals pre-treated chronically (21 days) with tolfenamic acid. The effects of amyloid beta micro-injected into the olfactory bulbs were also tested, after two weeks, on olfactory bulb population activity and olfaction in control and tolfenamic acid chronically treated animals. Olfaction was assessed with the odor-avoidance and the habituation/cross-habituation tests. GSK3β activation was evaluated with Western-blot. Results: Acute bath application of tolfenamic acid does not prevent amyloid beta-induced inhibition of olfactory bulb network activity in vitro. In contrast, chronic treatment with tolfenamic acid renders the olfactory bulb resistant to amyloid beta-induced network activity inhibition in vitro and in vivo, which correlates with the inhibition of GSK3β activation and the protection against amyloid beta-induced olfactory dysfunction. Conclusion: Our data further support the use of tolfenamic acid to prevent amyloid beta-induced pathology and the early symptoms of Alzheimer Disease.

scholarly journals The Role of EGCG in Breast Cancer Prevention and Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Adriana Romano ◽  
Fátima Martelb
Keyword(s):  
Breast Cancer ◽  
Cancer Prevention ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
Breast Cancer Prevention ◽  
Protective Effects ◽  
Experimental Conditions ◽  
Prevention And Therapy

Background: Breast cancer is the most frequent cancer in women. Green tea has been studied for breast cancer chemopreventive and possibly chemotherapeutic effects due to its high content in polyphenolic compounds, including epigallocatechin-3-gallate (EGCG). Method: This review is based on a literature research that included papers registered on the Medline database. The research was conducted through PubMed, with the application of the following query: “EGCG”AND "breast cancer”. The result was a total of 88 articles in which this review stands on. Results: In vitro, EGCG shows antioxidant or pro-oxidant properties, depending on the concentration and exposure time. EGCG blocks cell cycle progression and modulates signaling pathways that affects cell proliferation and differentiation. EGCG also induces apoptosis, negatively modulates different steps involved in metastasis and targets angiogenesis by inhibiting VEGF transcription. In vivo, investigations have shown that oral administration of EGCG results in reduction of tumor growth and in antimetastatic and antiangiogenic effects in animal xenograft and allograft models. Discussion: Much remains unknown about the molecular mechanisms involved in the protective effects of EGCG on mammary carcinogenesis. In addition, more studies in vivo are necessary to determine the potential toxicity of EGCG at higher doses and to elucidate its interactions with other drugs. Conclusion: A protective effect of EGCG has been shown in different experimental models and under different experimental conditions, suggesting clinical implications of EGCG for breast cancer prevention and therapy. The data presented in this review support the importance of further investigations.

Carnosine and Lung Disease

2020 ◽  
Vol 27 (11) ◽  
pp. 1714-1725 ◽  
Author(s):  
Ken-Ichiro Tanaka ◽  
Masahiro Kawahara
Keyword(s):  
Lung Disease ◽  
Metal Ion ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Protective Mechanisms ◽  
Low Levels ◽  
Metal Ion Chelation ◽  
Related Compounds

Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous activities, including antioxidant effects, metal ion chelation, proton buffering capacity, and inhibitory effects on protein carbonylation and glycation. Carnosine has been mostly studied in organs where it is abundant, including skeletal muscle, cerebral cortex, kidney, spleen, and plasma. Recently, the effect of supplementation with carnosine has been studied in organs with low levels of carnosine, such as the lung, in animal models of influenza virus or lipopolysaccharide-induced acute lung injury and pulmonary fibrosis. Among the known protective effects of carnosine, its antioxidant effect has attracted increasing attention for potential use in treating lung disease. In this review, we describe the in vitro and in vivo biological and physiological actions of carnosine. We also report our recent study and discuss the roles of carnosine or its related compounds in organs where carnosine is present in only small amounts (especially the lung) and its protective mechanisms.

FEEDING VALUE OF FORAGE AS FED TO STEERS AND ESTIMATED BY IN VITRO DIGESTION

1970 ◽  
Vol 50 (3) ◽  
pp. 547-555 ◽  
Author(s):  
J. E. TROELSEN ◽  
S. E. BEACOM
Keyword(s):  
Body Weight Gain ◽  
In Vitro Digestion ◽  
Experimental Conditions ◽  
Wide Range ◽  
Digestible Organic Matter ◽  
Feeding Value ◽  
Voluntary Intake ◽  
Highly Correlated

The digestibility and intake of 23 hays and three silages were determined in two experiments with Hereford steers averaging 215 kg at the start of the test. Each forage was fed in a chopped (4 to 6 cm) form as the sole diet to two steers for 56 days. Voluntary intake and body weight gain during the fourth through the seventh week were used as measures of animal performance. Digestibility was determined by collecting all the feces during the eighth week, allowing for a three-day lag between intake and excretion. The forages included grass, legume and cereal hays, and cereal and legume cereal silages produced under a wide range of conditions. The concentration of in vitro digestible organic matter (DOM) in the forage was highly correlated with gain (r = 0.57 and 0.86) and intake of digestible energy (DE) (r = 0.62 and 0.89). The voluntary intake by the steers was comparable with that by sheep in earlier experiments at two other locations, when the intake was based on metabolic body size, and on similar in vitro DOM or in vivo DE concentrations in the forage. Differences in intake between experiments followed the same pattern as feed allowance in excess of intake, but the effect of in vitro DOM or in vivo DE content on intake was apparently the same in each experiment. This supported the theory that regressions of DE intake by sheep on in vitro DOM content of forage will serve as a measure of the feeding value, providing that appropriate experimental conditions are maintained.

scholarly journals Gastroprotective Effects of Periplaneta americana L. Extract Against Ethanol-Induced Gastric Ulcer in Mice by Suppressing Apoptosis-Related Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Shu Fu ◽  
Jiamei Chen ◽  
Chen Zhang ◽  
Jinfeng Shi ◽  
Xin Nie ◽  
...  
Keyword(s):  
Cell Death ◽  
Gastric Ulcer ◽  
Programmed Cell Death ◽  
Periplaneta Americana ◽  
Periodic Acid ◽  
Protective Effects ◽  
Periodic Acid Schiff ◽  
Wide Range

Although Periplaneta americana L. and its modern preparation, Kangfuxin liquid, have been extensively applied for ulcerative diseases in gastrointestinal tract (e.g., gastric ulcer (GU) and ulcerative colitis, the effective components and potential mechanisms) remain unclear. In accordance with the accumulating research evidences, the relieving/exacerbating of GU is noticeably correlated to focal tissue programmed cell death. Herein, gastro-protective effects of the effective Periplaneta americana L. extract (PAE) fraction were assessed in vitro and in vivo, involving in programmed cell death-related signaling channels. To screen the effective PAE fraction exerting gastroprotective effects, several PAE fractions were gained based on a wide range of ethanol solution concentration, and they were assessed on ethanol-induced ulcer mice. Based on HPLC investigation with the use of nucleosides, the chemical composition of screened effective PAE, extracted by 20% ethanol, was analyzed in terms of quality control. Based on CCK-8 assay, the protective effects on GES-1 cells, impaired by ethanol, of PAE were assessed. After 3 days pre-treatment with PAE (200, 400, 800 mg/kg), the gastric lesions were assessed by tissue morphology, and periodic acid-schiff (PAS) staining, as well as hematoxylin and eosin (H&E) based histopathology-related investigation. The levels for inflammation cytokines (IL1-β, TNF-α, IL-18, PGE2, and IL-6), antioxidant indices (SOD and MDA) were examined via ELISA. In the meantime, based on Western Blotting assay, the expression levels of some programmed cell death-related protein targets (NLRP3, caspase-1, NF-κB p65, MyD88, and TLR4) were analyzed. As revealed from the results, PAE is capable of alleviating gastric mucosa impairment, suppressing the inflammatory cytokines, and down-regulating the MyD88/NF-κB channels. Accordingly, 20% ethanol extract of Periplaneta americana L. would contribute its gastroprotective effects, thereby providing the evidence that its anti-GU mechanisms correlated with inhibiting programmed cell death channel.

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