scholarly journals Optimized-SopungSunkiwon, a Herbal Formula, Attenuates AβOligomer-Induced Neurotoxicity in Alzheimer’s Disease Models

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin Gyu Choi ◽  
Sun Yeou Kim ◽  
Jong Woo Kim ◽  
Myung Sook Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Medicinal Herbs ◽  
Glutathione Depletion ◽  
Age Related

Alzheimer’s disease (AD), the most common form of dementia, is an age-related neurodegenerative disease that is characterized by memory dysfunction, neuronal cell damage, and neuroinflammation. It is believed that AD-related pathology is mostly due to the overproduction of Aβ, especially the oligomeric form (AβO), in the brain. Evidence of the effects of multifunctional medicinal herbs in the treatment of AD has been steadily increasing. Optimized-SopungSunkiwon (OSS), a multiherbal formulation that is composed of six medicinal herbs derived from SopungSunkiwon, is a traditional medicine that is prescribed for neurodegenerative disorders in elderly patients. We previously reported that OSS showed an antiamnesic and memory enhancing effect in mice, but it is unknown whether OSS has a protective effect against AβO neurotoxicity. In this study, we investigated the effects of OSS in AD models induced by AβOin vitroandin vivo. We found that OSS protected neuronal cells and inhibited the generation of nitric oxide and reactive oxygen species against AβO toxicityin vitro. These results were confirmed byin vivodata that oral administration of OSS for 14 days attenuated memory impairments and neuronal cell death by modulating gliosis, glutathione depletion, and synaptic damage in the mouse hippocampus induced by AβO.

scholarly journals The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rosmarinus Officinalis ◽  
Brain Inflammation ◽  
Important Species

Rosemary (Rosmarinus officinalisL.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents bothin vitroandin vivo. The therapeutic potential of these compounds for Alzheimer’s disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed.

scholarly journals SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer’s Disease Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1275
Author(s):  
Soo Yong Park ◽  
Joo Yeong Kang ◽  
Taehee Lee ◽  
Donggyu Nam ◽  
Chang-Jin Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Physiological Activity ◽  
Precursor Protein ◽  
Age Related

Alzheimer’s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aβ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aβ reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aβ in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aβ and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.

scholarly journals Direct and Indirect Roles of Cyclin-dependent Kinase 5 as an Upstream Regulator in the c-Jun NH2-Terminal Kinase Cascade: Relevance to Neurotoxic Insults in Alzheimer's Disease

2009 ◽  
Vol 20 (21) ◽  
pp. 4611-4619 ◽  
Author(s):  
Kai-Hui Sun ◽  
Hyoung-gon Lee ◽  
Mark A. Smith ◽  
Kavita Shah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Second Phase ◽  
Jnk Pathway ◽  
Upstream Regulator ◽  
Kinase Cascade

Significant increase in JNK, c-Jun, and Cdk5 activities are reported in Alzheimer's disease (AD). Inhibition of c-Jun prevents neuronal cell death in in vivo AD models, highlighting it as a major JNK effector. Both JNK and Cdk5 promote neurodegeneration upon deregulation; however, Cdk5 has not been mechanistically linked to JNK or c-Jun. This study presents the first mechanism showing Cdk5 as a major regulator of the JNK cascade. Deregulated Cdk5 induces biphasic activation of JNK pathway. The first phase revealed c-Jun as a direct substrate of Cdk5, whose activation is independent of reactive oxygen species (ROS) and JNK. In the second phase, Cdk5 activates c-Jun via ROS-mediated activation of JNK. Rapid c-Jun activation is supported by in vivo data showing c-Jun phosphorylation in cerebral cortex upon p25 induction in transgenic mice. Cdk5-mediated biphasic activation of c-Jun highlights c-Jun, rather than JNK, as an important therapeutic target, which was confirmed in neuronal cells. Finally, Cdk5 inhibition endows superior protection against neurotoxicity, suggesting that Cdk5 is a preferable therapeutic target for AD relative to JNK and c-Jun.

scholarly journals Bacopa monnierias an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tamara Simpson ◽  
Matthew Pase ◽  
Con Stough
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Bacopa Monnieri ◽  
Aging Brain ◽  
Resonance Spectroscopy ◽  
Age Related

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herbBacopa monnieriis a dietary antioxidant, with animal andin vitrostudies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts ofBacopa monnieriimprove cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies andin vivoevidence forBacopa monnierias a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant statusin vivocause improvements in cognitive function.

scholarly journals Recent updates on the role of herbal medicine for Alzheimer's disease (Dementia)

2021 ◽  
Vol 8 (1) ◽  
pp. 14-45
Author(s):  
Ravindra B. Malabadi ◽  
Kiran P. Kolkar ◽  
Neelambika T. Meti ◽  
Raju K. Chalannavar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Herbal Medicine ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Disorder ◽  
Cognitive Changes ◽  
Potent Effect ◽  
Age Related

This review paper highlights the use of medicinal plants in the management of Alzheimer's disease and memory deficit. Alzheimer’s disease is the most common form of dementia, a serious brain disorder that impacts daily living through memory loss and cognitive changes. Alzheimer's disease is also age-related neurodegenerative disorders caused by progressive loss of structure or function of neurons, resulting in neuronal cell death. Alzheimer's patients have an acetylcholine deficiency. Stressful conditions, free radicle scavanging and oxidation are often associated with loss of memory and cognitive functions, which may lead to threats of schizophrenia and Alzheimer's disease. However, the use of allopathic drugs has resulted in the adverse side effects on the human body and thus limits the use of such drugs. Herbal cognitive enhancer drugs have shown their potent effect in Alzheimer’s disease due to their antioxidant and neuropharmacological actions. The use of natural cognitive enhancers evidenced to improve mental functions such as cognition, memory, intelligence, motivation, attention and concentration. Traditional Ayurvedic herbal system of medicine is fundamentally preventive, protective, nutritive, curative and less expensive. Therefore, the use of herbal medicine for the treatment of Alzheimer's disease is a novel approach without any side effects.

scholarly journals The Combination of β-Asarone and Icariin Inhibits Amyloid-β and Reverses Cognitive Deficits by Promoting Mitophagy in Models of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Nanbu Wang ◽  
Haoyu Wang ◽  
Qi Pan ◽  
Jian Kang ◽  
Ziwen Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combination Therapy ◽  
Cognitive Deficits ◽  
Amyloid Β ◽  
In Vivo Models ◽  
Age Related ◽  
The Individual

β-Asarone is the main constituent of Acorus tatarinowii Schott and exhibits important effects in diseases such as neurodegenerative and neurovascular diseases. Icariin (ICA) is a major active ingredient of Epimedium that has attracted increasing attention because of its unique pharmacological effects in degenerative disease. In this paper, we primarily explored the effects of the combination of β-asarone and ICA in clearing noxious proteins and reversing cognitive deficits. The accumulation of damaged mitochondria and mitophagy are hallmarks of aging and age-related neurodegeneration, including Alzheimer’s disease (AD). Here, we provide evidence that autophagy/mitophagy is impaired in the hippocampus of APP/PS1 mice and in Aβ1-42-induced PC12 cell models. Enhanced mitophagic activity has been reported to promote Aβ and tau clearance in in vitro and in vivo models. Meanwhile, there is growing evidence that treatment of AD should be preceded by intervention before the formation of pathological products. The efficacy of the combination therapy was better than that of the individual therapies applied separately. Then, we found that the combination therapy also inhibited cell and mitochondrial damage by inducing autophagy/mitophagy. These findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis, and that combination treatment with mitophagy inducers represents a potential strategy for therapeutic intervention.

scholarly journals Computer-assisted evaluation of plant-derived β-secretase inhibitors in Alzheimer’s disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Md. Asad Ullah ◽  
Fatema Tuz Johora ◽  
Bishajit Sarkar ◽  
Yusha Araf ◽  
Nafisa Ahmed ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Biological Activities ◽  
Memory Loss ◽  
Computer Assisted ◽  
Age Related ◽  
Secretase Inhibitor

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative age-related dementia that results in memory loss of elderly people. Many hypotheses have been formally articulated till now to decipher the pathogenesis of this disease. According to the compelling amyloidogenic hypothesis, β-secretase is a key regulatory enzyme in AD development and is therefore considered as one of the major targets for the development of drugs to treat AD. In this study, 40 plant-derived phytocompounds, proven to have β-secretase inhibitory activity in different laboratory experiments, were evaluated using computational approaches in order to identify the best possible β-secretase inhibitor(s). Results Amentoflavone (IFD score: − 7.842 Kcal/mol), Bilobetin (IFD score: − 7.417 Kcal/mol), and Ellagic acid (IFD score: − 6.923 Kcal/mol) showed highest β-secretase inhibitory activities with high binding affinity among all the selected phytocompounds and interacted with key amino acids, i.e., Asp32, Tyr71, and Asp228 in the catalytic site of β-secretase. Moreover, these three molecules exhibited promising results in different drug potential assessment experiments and displayed signs of correlation with significant pharmacological and biological activities. Conclusion Amentoflavone, Biolbetin, and Ellagic acid could be investigated further in developing β-secretase-dependent drug for the effective treatment of AD. However, additional in vivo and in vitro experiments might be required to strengthen the findings of this experiment.

Survival signalling in Alzheimer's disease

2006 ◽  
Vol 34 (6) ◽  
pp. 1277-1282 ◽  
Author(s):  
W.J. Lukiw ◽  
N.G. Bazan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acid ◽  
Cell Survival ◽  
Plasma Membranes ◽  
Enzymatic System ◽  
Neuroprotectin D1 ◽  
Age Related

Significant advancements in our understanding of cell-survival signalling in AD (Alzheimer's disease) stem from recent investigations into the metabolism, trafficking and fate of the essential ω-3 fatty acid DHA (docosahexaenoic acid) (C22:6, n=3). Brain synaptic terminals and neuronal plasma membranes are highly enriched in DHA, and deficiencies in this polyunsaturated fatty acid are characteristic of AD-affected brain. Oxidative stress, targeting phospholipids containing DHA, and age-related DHA depletion are associated with the progressive erosion of normal cognitive function in AD. Current studies support the idea that DHA itself and novel DHA-derived neural synapse- and membrane-derived lipid messengers have considerable potential to modulate cell survival signalling in stressed cultured neural cell models in vitro and in mammalian models of learning, memory and AD in vivo. Key players in this intrinsic rescue system include the α-secretase-processed neurotrophin sAPPα [soluble APPα (amyloid precursor protein α)] peptide, the DHA-derived 10,17S-docosatriene NPD1 (neuroprotectin D1), a tandem brain cytosolic phospholipase A2 and 15-lipoxygenase enzymatic system that biosynthesizes NPD1, and a small family of anti-apoptotic neuroprotective genes that encode Bcl-2, Bcl-XL and Bfl-1 (A1). This paper reviews current ideas regarding DHA and the oxygenated DHA derivative NPD1, intrinsically triggered biolipid neuroprotectants that along with their associated rescue pathways, contribute to life-or-death decisions of brain cells during homoeostasis, aging and neurodegenerative disease.

Aromatase/Seladin-1 Interactions in Human Neuronal Cell Culture, the Hippocampus of Healthy Rats and Transgenic Alzheimer’s Disease Mice

Pharmacology ◽  
2018 ◽  
Vol 102 (1-2) ◽  
pp. 42-52 ◽  
Author(s):  
Hande Karahan ◽  
Sevda Lüle ◽  
Pelin Kelicen-Uğur
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Human Neuroblastoma ◽  
Protein Levels ◽  
Genes Encoding ◽  
Estrogen Biosynthesis

Background/Aims: Decreasing levels of aromatase and seladin-1 could be one of the molecular mechanisms of Alzheimer’s disease (AD). Aromatase is an enzyme that catalyzes estrogen biosynthesis from androgen precursors, and seladin-1 is an enzyme that converts desmosterol to cholesterol, which is the precursor of all hormones. Verifying the potential relationship between these proteins and accordingly determining new therapeutic targets constitute the aims of this study. Methods: Changes in protein levels were compared in vitro in aromatase and seladin-1 inhibitor-administered human neuroblastoma (SH-SY5Y) cells in vivo in intracerebroventricular (icv) aromatase or seladin-1 inhibitor-administered rats, as well as in transgenic AD mice in which the genes encoding these proteins were knocked out. Results and Conclusions: In the cell cultures, we observed that seladin-1 protein levels increased after aromatase enzyme inhibition. The hippocampal aromatase protein levels decreased following chronic seladin-1 inhibition in icv inhibitor-administered rats; however, the aromatase levels in the dentate gyrus of seladin-1 knockout (SelKO) AD male mice increased. These findings indicate a partial relationship between these proteins and their roles in AD pathology.

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