scholarly journals A UPLC-Q-TOF/MS-Based Metabolomics Study on the Effect of Corallodiscus flabellatus (Craib) B. L. Burtt Extract on Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yang-Yang Wang ◽  
Ning Zhou ◽  
Yan-Po Si ◽  
Zhi-Yao Bai ◽  
Meng Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolite Profiling ◽  
Huperzine A ◽  
Control Group ◽  
Model Group ◽  
Metabolomics Study ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Tof Ms

A UPLC-Q-TOF/MS-based metabolomics study was carried out to explore the intervening mechanism of Corallodiscus flabellatus (Craib) B. L. Burtt (CF) extract on Alzheimer’s disease (AD). The AD model group consisted of senescence-accelerated mouse prone 8 (SAMP8) mice, and the control group consisted of senescence-accelerated mouse resistant 1 (SAMR1) mice. UPLC-Q-TOF/MS detection, multivariate statistical analysis, and pathway enrichment were jointly performed to research the change in metabolite profiling in the urine of AD mice. The result suggested that the metabolite profiling of SAMP8 mice significantly changed at the sixth month compared with SAMR1 mice of the same age, and the principal component analysis (PCA) score scatter plots of the CF group closely resembled those of the control and positive drug (huperzine A, HA) group. A total of 28 metabolites were considered potential biomarkers associated with the metabolism of beta-alanine, glycine, serine, threonine, cysteine, methionine, arginine, proline, and purines in AD mice. Furthermore, the CF group was clustered with the control and positive group and was clearly separated from the model group in the heat map. In conclusion, significant anti-AD effects were firstly observed in mice after treatment with the CF extract, and the urinary metabolomics approach assisted with dissecting the underlying mechanism.

The Clinical Analysis of Combined Effects of Huperzine A and Memantine for Alzheimer’s Disease

2011 ◽  
pp. 112-116
Author(s):  
Shouzi Zhang ◽  
Qinyun Li ◽  
Maolong Gao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treated Group ◽  
Clinical Analysis ◽  
Huperzine A ◽  
Control Group ◽  
Clinical Effects ◽  
Activity Of Daily Living ◽  
State Examination ◽  
Target Activity

The purpose of this study was to evaluate the clinical effects of a combination of Huperzine A and memantine for the treatment of Alzheimer’s disease (AD). Sixty patients (aged 69 ± 4.5), treated in both outpatient and hospital settings, were divided into two groups, the treated group and the control group. Over 24 weeks of clinical therapy, 30 patients received treatment with Huperzine A (0.2 mg/d), and the other 30 patients received a combination of Huperzine A (0.2 mg/d) and memantine (20 mg/d). Mini-mental State Examination (MMSE) was taken as the main value target. Activity of Daily Living Scale (ADL) and Neuropsychiatric Inventory (NPI) were secondary targets. Results: After 24 weeks, the scores from the MMSE, ADL, and NPI of the treatment group were more improved than those of the control group (P=0.05). Combination treatment with Huperzine A and memantine will be more effective for treating AD than treatment with Huperzine A alone.

A UPLC-TOF/MS-based metabolomics study of rattan stems ofSchisandra chinensiseffects on Alzheimer's disease rats model

2017 ◽  
Vol 32 (2) ◽  
pp. e4037 ◽  
Author(s):  
Bing-You Yang ◽  
Jin-Yan Tan ◽  
Yan Liu ◽  
Bo Liu ◽  
Shuang Jin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolomics Study ◽  
Tof Ms

scholarly journals Trimethylamine N-Oxide (TMAO) links peripheral insulin resistance and cognitive deficiencies in a senescence accelerated mouse model

2021 ◽  
Author(s):  
Manuel H. Janeiro ◽  
Elena Puerta ◽  
Maria Lanz ◽  
Fermin I. Milagro ◽  
Maria J Ramirez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Insulin Signaling ◽  
Samp8 Mouse ◽  
Cognitive Deficiencies ◽  
Samp8 Mice ◽  
The Brain ◽  
Senescence Accelerated Mouse

It has been established that ageing is the major risk factor for cognitive deficiency or neurodegenerative diseases such as Alzheimer's disease (AD) and it is becoming increasingly evident that insulin resistance is another factor. Biological plausibility for a link between insulin resistance and dementia is relevant for understanding disease etiology, and to form bases for prevention efforts to decrease disease burden. The dysfunction of the insulin signaling system and glucose metabolism has been proposed to be responsible for brain aging. Normal insulin signaling in the brain is required to mediate growth, metabolic functions, and the survival of neurons and glia. Insulin receptors are densely expressed in the olfactory bulb, the cerebral cortex and the hippocampus and regulate neurotransmitter release and receptor recruitment. In normal elderly individuals, reduced glucose tolerance and decreased insulin levels in the aged brain are typically observed. Furthermore, insulin signaling is aberrantly activated in the AD brain, leading to non-responsive insulin receptor signaling. The senescence accelerated mouse (SAMP8) mouse was one of the accelerated senescence strains that spontaneously developed from breeding pairs of the AKR/J series. The SAMP8 mouse develops early learning and memory deficits (between 6 and 8 months) together with other characteristics similar to those seen in Alzheimer's disease. The present project proposes the investigation of the missing link between aging, insulin resistance and dementia. Peripheral but not central insulin resistance was found in SAMP8 mice accompanied by cognitive deficiencies. Furthermore, a marked peripheral inflammatory state (i.e. significantly higher adipose tissue TNF-[alpha]; and IL6 levels) were observed in SAMP8 mice, followed by neuroinflammation that could be due to a higher cytokine leaking into the brain across a aging-disrupted BBB. Moreover, aging-induced gut dysbiosis produces higher TMAO that could also contribute to the peripheral and central inflammatory tone as well as to the cognitive deficiencies observed in SAMP8 mice. All those alterations were reversed by DMB, a treatment inhibits the transformation of choline, carnitine and crotonobetaine, decreaseing TMAO levels. The ever-increasing incidence of neurodegenerative diseases not only limits the life quality of the affected individuals and their families but also poses an enormous demand on the societies. Thus, it is instrumental to pursue novel promising approaches to prevent and treat it at the highest possible speed to rapidly translate them to clinical practice. From this point of view, data obtained from this project will be instrumental to validate the principle approach of microbial dysbiosis and increased TMAO secretion as a key link between aging, insulin resistance and dementia. Collectively, the proposed experiments ideally integrate the aim to promote a novel approach to improve the lives of those suffering from cognitive disturbances.

scholarly journals Effects of Phenylethanoid Glycosides Extracted from Herba Cistanches on the Learning and Memory of the APP/PSI Transgenic Mice with Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jianhua Yang ◽  
Bowei Ju ◽  
Junping Hu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Active Components ◽  
Phenylethanoid Glycosides ◽  
Step Down

Background. To investigate the effects of phenylethanoid glycosides (PhGs) extracted from Herba Cistanches on the behavioral and cognition capacity of the APP/PSI transgenic mice with Alzheimer’s disease (AD). Methods. AD mice were randomly divided into the control group, model group, donepezil group, PhG groups, and verbascose group, respectively. Three weeks later, the animals were subject to behavioral and cognition evaluation by the nesting test, Morris water maze test, and step-down test. Results. The cognition capacity in these groups showed a significant increase compared with that in the model group. The step-down test indicated that the errors induced by the memory decrease in the PhG groups and verbascose group showed a significant decrease compared with those in the model group ( P < 0.05 ). Conclusions. PhGs attenuated the cognitive dysfunction features of the APP/PSI transgenic gene. Besides, PhGs were the active components for the anti-AD activity of H. Cistanches.

scholarly journals Evaluation of SAMP8 Mice as a Model for Sleep-Wake and Rhythm Disturbances Associated with Alzheimer’s Disease: Impact of Treatment with the Dual Orexin (Hypocretin) Receptor Antagonist Lemborexant

2021 ◽  
pp. 1-17
Author(s):  
Carsten T. Beuckmann ◽  
Hiroyuki Suzuki ◽  
Erik S. Musiek ◽  
Takashi Ueno ◽  
Toshitaka Sato ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythm ◽  
Receptor Antagonist ◽  
Diurnal Rhythm ◽  
Rem Sleep ◽  
Running Wheel ◽  
Wheel Activity ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

Background: Many patients with Alzheimer’s disease (AD) display circadian rhythm and sleep-wake disturbances. However, few mouse AD models exhibit these disturbances. Lemborexant, a dual orexin receptor antagonist, is under development for treating circadian rhythm disorders in dementia. Objective: Evaluation of senescence-accelerated mouse prone-8 (SAMP8) mice as a model for sleep-wake and rhythm disturbances in AD and the effect of lemborexant by assessing sleep-wake/diurnal rhythm behavior. Methods: SAMP8 and control senescence-accelerated mouse resistant-1 (SAMR1) mice received vehicle or lemborexant at light onset; plasma lemborexant and diurnal cerebrospinal fluid (CSF) orexin concentrations were assessed. Sleep-wake behavior and running wheel activity were evaluated. Results: Plasma lemborexant concentrations were similar between strains. The peak/nadir timing of CSF orexin concentrations were approximately opposite between strains. During lights-on, SAMP8 mice showed less non-rapid eye movement (non-REM) and REM sleep than SAMR1 mice. Lemborexant treatment normalized wakefulness/non-REM sleep in SAMP8 mice. During lights-off, lemborexant-treated SAMR1 mice showed increased non-REM sleep; lemborexant-treated SAMP8 mice displayed increased wakefulness. SAMP8 mice showed differences in electroencephalogram architecture versus SAMR1 mice. SAMP8 mice exhibited more running wheel activity during lights-on. Lemborexant treatment reduced activity during lights-on and increased activity in the latter half of lights-off, demonstrating a corrective effect on overall diurnal rhythm. Lemborexant delayed the acrophase of activity in both strains by approximately 1 hour. Conclusion: SAMP8 mice display several aspects of sleep-wake and rhythm disturbances in AD, notably mistimed activity. These findings provide some preclinical rationale for evaluating lemborexant in patients with AD who experience sleep-wake and rhythm disturbances.

scholarly journals Electroacupuncture Could Influence the Expression of IL-1β and NLRP3 Inflammasome in Hippocampus of Alzheimer’s Disease Animal Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Jiang ◽  
Ning Ding ◽  
Kang Wang ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Nlrp3 Inflammasome ◽  
Day Treatment ◽  
Control Group ◽  
Acupuncture Points ◽  
Spatial Learning And Memory ◽  
Caspase 1 ◽  
Samp8 Mice

Background. Effective therapies for Alzheimer’s disease (AD) are still being explored. Electroacupuncture with traditional Chinese medicine theory may improve spatial learning and memory abilities and glucose metabolism rates in an animal model of AD. However, the mechanism of electroacupuncture in intervention of AD is still unclear. According to recent studies of AD mechanisms, the NLRP3 inflammasome regulated the expression of IL-1β in the brain which may mediate AD related processes. Therefore, in our study, we intend to explore the possible relation between electroacupuncture and the expression of NLRP 3 inflammasome in the hippocampus of an AD animal model. Method. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an AD animal model, which were randomly divided into two groups: Alzheimer’s disease model group (AD group) and electroacupuncture group (EA group). In the control paradigm, 7.5-month-old male SAMR1 mice were used as the normal control group (N group). DU20, DU26, and EX-HN3 were selected as the acupuncture points, and after a 15-day treatment of electroacupuncture, we used immunohistochemistry and Western blotting to examine the expression of IL-1β and NLRP3, ASC, and Caspase-1 in the hippocampus of the AD animal model. Results. Compared with N group, IL-1β, NLRP3, ASC, and Caspase-1 positive cells in AD group were increased, and the relative expression of all above proteins significantly increased (P < 0.01). Compared with AD group, the expression of IL-1β, NLRP3, ASC, and Caspase-1 in EA group was significantly decreased (P < 0.01). Conclusion. Electroacupuncture treatment could inhibit the inflammation reaction in the hippocampus of SAMP8 mice. What is more, the possible mechanism of electroacupuncture reduced the expression of IL-1β and NLRP3 inflammasome relative protein.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

scholarly journals Endophytic Fungal Community of Huperzia serrata: Diversity and Relevance to the Production of Huperzine A by the Plant Host

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 892
Author(s):  
Lingli Cui ◽  
Hamza Armghan Noushahi ◽  
Yipeng Zhang ◽  
Jinxin Liu ◽  
Andreea Cosoveanu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fungal Community ◽  
Slow Growth ◽  
Specific Treatment ◽  
Huperzine A ◽  
Ionization Mass ◽  
Correlation Index ◽  
Plant Host ◽  
Huperzia Serrata

As the population ages globally, there seem to be more people with Alzheimer’s disease. Unfortunately, there is currently no specific treatment for the disease. At present, Huperzine A (HupA) is one of the best drugs used for the treatment of Alzheimer’s disease and has been used in clinical trials for several years in China. HupA was first separated from Huperzia serrata, a traditional medicinal herb that is used to cure fever, contusions, strains, hematuria, schizophrenia, and snakebite for several hundreds of years in China, and has been confirmed to have acetylcholinesterase inhibitory activity. With the very slow growth of H. serrata, resources are becoming too scarce to meet the need for clinical treatment. Some endophytic fungal strains that produce HupA were isolated from H. serrate in previous studies. In this article, the diversity of the endophytic fungal community within H. serrata was observed and the relevance to the production of HupA by the host plant was further analyzed. A total of 1167 strains were obtained from the leaves of H. serrata followed by the stems (1045) and roots (824). The richness as well as diversity of endophytic fungi within the leaf and stem were higher than in the root. The endophytic fungal community was similar within stems as well as in leaves at all taxonomic levels. The 11 genera (Derxomyces, Lophiostoma, Cyphellophora, Devriesia, Serendipita, Kurtzmanomyces, Mycosphaerella, Conoideocrella, Brevicellicium, Piskurozyma, and Trichomerium) were positively correlated with HupA content. The correlation index of Derxomyces with HupA contents displayed the highest value (CI = 0.92), whereas Trichomerium showed the lowest value (CI = 0.02). Through electrospray ionization mass spectrometry (ESI-MS), it was confirmed that the HS7-1 strain could produce HupA and the total alkaloid concentration was 3.7 ug/g. This study will enable us to screen and isolate the strain that can produce HupA and to figure out the correlation between endophytic fungal diversity with HupA content in different plant organs. This can provide new insights into the screening of strains that can produce HupA more effectively.

Sign in / Sign up

Export Citation Format

Share Document