scholarly journals GuanXinNing Tablet Attenuates Alzheimer’s Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Feng Zhang ◽  
Yanyun Xu ◽  
Liye Shen ◽  
Junjie Huang ◽  
Songtao Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neuronal Apoptosis ◽  
Chinese Herbs ◽  
16S Rrna Analysis ◽  
Serum Metabolites ◽  
Neuronal Metabolism ◽  
Guanxinning Tablet

Based on accumulating evidence, Alzheimer’s disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aβ), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aβ deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

scholarly journals Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Luca ◽  
Maurizio Di Mauro ◽  
Marco Di Mauro ◽  
Antonina Luca
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Therapeutic Implications

Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer’s disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer’s disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.

scholarly journals Ceramides in Alzheimer’s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and AβAccumulation

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Maja Jazvinšćak Jembrek ◽  
Patrick R. Hof ◽  
Goran Šimić
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Apoptosis ◽  
Neurodegenerative Disorder ◽  
Neuronal Degeneration ◽  
Sphingolipid Metabolism ◽  
Cytochrome C Release ◽  
Biochemical Alterations

Alzheimer’s disease (AD), the most common chronic and progressive neurodegenerative disorder, is characterized by extracellular deposits of amyloidβ-peptides (Aβ) and intracellular deposits of hyperphosphorylated tau (phospho-tau) protein. Ceramides, the major molecules of sphingolipid metabolism and lipid second messengers, have been associated with AD progression and pathology via Aβgeneration. Enhanced levels of ceramides directly increase Aβthrough stabilization ofβ-secretase, the key enzyme in the amyloidogenic processing of Aβprecursor protein (APP). As a positive feedback loop, the generated oligomeric and fibrillar Aβinduces a further increase in ceramide levels by activating sphingomyelinases that catalyze the catabolic breakdown of sphingomyelin to ceramide. Evidence also supports important role of ceramides in neuronal apoptosis. Ceramides may initiate a cascade of biochemical alterations, which ultimately leads to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria, increased production of reactive oxygen species (ROS), cytochrome c release, Bcl-2 depletion, and caspase-3 activation, mainly by modulating intracellular signalling, particularly along the pathways related to Akt/PKB kinase and mitogen-activated protein kinases (MAPKs). This review summarizes recent findings related to the role of ceramides in oxidative stress-driven neuronal apoptosis and interplay with Aβin the cascade of events ending in neuronal degeneration.

scholarly journals Krill Oil Attenuates Cognitive Impairment by the Regulation of Oxidative Stress and Neuronal Apoptosis in an Amyloid β-Induced Alzheimer’s Disease Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3942
Author(s):  
Ji Hyun Kim ◽  
Hui Wen Meng ◽  
Mei Tong He ◽  
Ji Myung Choi ◽  
Dongjun Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Neuronal Apoptosis ◽  
Morris Water Maze Test ◽  
Krill Oil ◽  
Cognitive Improvement ◽  
The Brain

In the present study, we investigated the cognitive improvement effects and its mechanisms of krill oil (KO) in Aβ25–35-induced Alzheimer’s disease (AD) mouse model. The Aβ25–35-injected AD mouse showed memory and cognitive impairment in the behavior tests. However, the administration of KO improved novel object recognition ability and passive avoidance ability compared with Aβ25–35-injected control mice in behavior tests. In addition, KO-administered mice showed shorter latency to find the hidden platform in a Morris water maze test, indicating that KO improved learning and memory abilities. To evaluate the cognitive improvement mechanisms of KO, we measured the oxidative stress-related biomarkers and apoptosis-related protein expressions in the brain. The administration of KO inhibited oxidative stress-related biomarkers such as reactive oxygen species, malondialdehyde, and nitric oxide compared with AD control mice induced by Aβ25–35. In addition, KO-administered mice showed down-regulation of Bax/Bcl-2 ratio in the brain. Therefore, this study indicated that KO-administered mice improved cognitive function against Aβ25–35 by attenuations of neuronal oxidative stress and neuronal apoptosis. It suggests that KO might be a potential agent for prevention and treatment of AD.

scholarly journals The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1370
Author(s):  
Umair Shabbir ◽  
Akanksha Tyagi ◽  
Fazle Elahi ◽  
Simon Okomo Aloo ◽  
Deog-Hwan Oh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Potential Role ◽  
Inflammatory Responses ◽  
Dietary Polyphenols ◽  
Gut Dysbiosis

Gut microbiota (GM) play a role in the metabolic health, gut eubiosis, nutrition, and physiology of humans. They are also involved in the regulation of inflammation, oxidative stress, immune responses, central and peripheral neurotransmission. Aging and unhealthy dietary patterns, along with oxidative and inflammatory responses due to gut dysbiosis, can lead to the pathogenesis of neurodegenerative diseases, especially Alzheimer’s disease (AD). Although the exact mechanism between AD and GM dysbiosis is still unknown, recent studies claim that secretions from the gut can enhance hallmarks of AD by disturbing the intestinal permeability and blood–brain barrier via the microbiota–gut–brain axis. Dietary polyphenols are the secondary metabolites of plants that possess anti-oxidative and anti-inflammatory properties and can ameliorate gut dysbiosis by enhancing the abundance of beneficial bacteria. Thus, modulation of gut by polyphenols can prevent and treat AD and other neurodegenerative diseases. This review summarizes the role of oxidative stress, inflammation, and GM in AD. Further, it provides an overview on the ability of polyphenols to modulate gut dysbiosis, oxidative stress, and inflammation against AD.

Oxidative Stress and Amyloid Beta Toxicity in Alzheimer’s Disease: Intervention in a Complex Relationship by Antioxidants

2013 ◽  
Vol 20 (37) ◽  
pp. 4648-4664 ◽  
Author(s):  
S. Chakrabarti ◽  
M. Sinha ◽  
I. Thakurta ◽  
P. Banerjee ◽  
M. Chattopadhyay
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Complex Relationship

Targeting PPARalpha in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Peroxisome Proliferator ◽  
Prevailing Paradigm

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

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