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https://www.readbyqxmd.com/read/28649615/imaging-parkinson-s-disease-below-the-neck
#1
Per Borghammer, Karoline Knudsen, Tatyana D Fedorova, David J Brooks
Parkinson's disease is a systemic disorder with widespread and early α-synuclein pathology in the autonomic and enteric nervous systems, which is present throughout the gastrointestinal canal prior to diagnosis. Gastrointestinal and genitourinary autonomic symptoms often predate clinical diagnosis by several years. It has been hypothesized that progressive α-synuclein aggregation is initiated in hyperbranched, non-myelinated neuron terminals, and may subsequently spread via retrograde axonal transport. This would explain why autonomic nerves are so prone to formation of α-synuclein pathology...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28634862/effect-of-gapt-extract-on-expression-of-tau-protein-and-its-phosphorylation-related-enzymes-in-hippocampal-neurons-of-appv717i-transgenic-mice
#2
Jing-Nian Ni, Jing Shi, Xue-Kai Zhang, Yi-Chang Yang, Xiao-Meng Liu, Ming-Qing Wei, Ting Li, Peng-Wen Wang, Jin-Zhou Tian, Yong-Yan Wang
OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg d)], the low, medium and high dosage of GAPT groups [0...
June 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28618650/anti-amnesic-effects-of-ganoderma-species-a-possible-cholinergic-and-antioxidant-mechanism
#3
Ravneet Kaur, Varinder Singh, Richa Shri
Mushrooms are valued for their nutritional as well as medicinal properties. Ganoderma species are used traditionally to treat neurological disorders but scientific evidence for this is insufficient. The present study was designed to systematically evaluate the anti-amnesic effect of selected Ganoderma species i.e. G. mediosinense and G. ramosissimum. Extracts of selected mushroom species were evaluated for their antioxidant activity and acetylcholinesterase (AChE) inhibition using in-vitro assays (DPPH and Ellman tests respectively)...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28613859/donepezil-based-central-acetylcholinesterase-inhibitors-by-means-of-a-bio-oxidizable-prodrug-strategy-design-synthesis-and-in-vitro-biological-evaluation
#4
Ludovic Peauger, Rabah Azzouz, Vincent Gembus, Mihaela-Liliana Tintas, Jana Sopková-de Oliveira Santos, Pierre Bohn, Cyril Papamicaël, Vincent Levacher
With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new class of donepezil-based "bio-oxidizable" prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC50 up to 3 nM), outperforming the standard drug donepezil (IC50 = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive...
June 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28603119/effect-of-chongmyungtang-a-traditional-korean-polyherbal-formula-on-the-pharmacokinetic-profiles-of-donepezil-in-rats
#5
Kyung-Min Baek, Oh-Dae Kwon, Soo-Jin Park, Chang-Hyun Song, Sae-Kwang Ku
Chongmyungtang (CMT) is a famous Korean herbal medicine for improving learning and memory, which has been reported to have anti-cholinergic and neuroprotective effects. Therefore, drug-drug interactions were examined between CMT and donepezil as a first screening of combination therapy for cognitive deficits. Rats received oral co-administration of donepezil with distilled water as a control or donepezil with CMT as a combination. The distilled water or CMT was co-administered at intervals within 5min after donepezil or 1...
January 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28596794/efficacy-and-safety-of-an-herbal-therapy-in-patients-with-amnestic-mild-cognitive-impairment-a-24-week-randomized-phase-iii-trial
#6
Jinzhou Tian, Jing Shi, Tao Li, Lin Li, Zhiliang Wang, Xiaobin Li, Zhu Lv, Qingshan Zheng, Mingqing Wei, Yongyan Wang
OBJECTIVE: In the 24-week randomized, double-blind, double-placebo, parallel-controlled trial, we aimed to test the effects of herbal therapy with amnestic mild cognitive impairment (aMCI). METHODS: A total of 324 patients with aMCI entered a 2-week placebo run-in period followed by 24 weeks' treatment of either (a) herbal capsule (5 shenwu capsules/administration, 3 times/day) and placebo identical to donepezil tablets (n = 216) or (b) donepezil (5 mg/day) and placebo identical to herbal capsule (n = 108)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28590369/adverse-events-with-sustained-release-donepezil-in-alzheimer-disease-relation-to-body-mass-index
#7
Chunsoo Lee, Kyungsang Lee, Hyewon Yu, Seung-Ho Ryu, Seok Woo Moon, Changsu Han, Jun-Young Lee, Young Min Lee, Shin-Gyeom Kim, Ki Woong Kim, Dong Woo Lee, Seong Yoon Kim, Sang-Yeol Lee, Jae Nam Bae, Young-Eun Jung, Jeong Lan Kim, Byung-Soo Kim, Il-Seon Shin, Young Hoon Kim, Bong Jo Kim, Hyo Shin Kang, Woojae Myung, Bernard J Carroll, Doh Kwan Kim
PURPOSE/BACKGROUND: Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. METHODS/PROCEDURES: To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months...
August 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28588366/neurocognitive-effect-of-nootropic-drug-brahmi-bacopa-monnieri-in-alzheimer-s-disease
#8
REVIEW
Kaustubh S Chaudhari, Nishant R Tiwari, Rakesh R Tiwari, Rohan S Sharma
Alzheimer's disease (AD) is a progressive neurodegenerative disease of the elderly. The rapid increase in its incidence has necessitated development of newer drugs. Ayurvedic herbal medications are increasingly researched due to their biosafety profile and usefulness in cognitive impairment. In this article, we critically reviewed one such Medhya Rasayana (nootropic drug) Brahmi-derived from extract of Bacopa monnieri (EBm). Studies have shown that EBm promotes free radical scavenger mechanisms and protects cells in prefrontal cortex, hippocampus, and striatum against cytotoxicity and DNA damage implicated in AD...
May 2017: Annals of Neurosciences
https://www.readbyqxmd.com/read/28576405/protective-effects-of-donepezil-against-endothelial-permeability
#9
Xuelu Tang, Xiuhua Di, Yilin Liu
The endothelium lines the interior surface of blood vessels, and under pathophysiologic conditions, its integrity can be compromised due to a disturbance in the expression of tight junctions. Donepezil is a licensed drug used in the palliative treatment of Alzheimer's disease (AD). Increasing evidence has reported that donepezil has an anti-inflammatory activity. However, little information is available regarding the role of donepezil in vascular diseases. In this study, we found that pretreatment with donepezil significantly ameliorated endothelial permeability induced by tumor necrosis factor (TNF-α) by restoring the expression of the tight junction proteins vascular endothelial cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in human umbilical vein endothelial cells (HUVECs)...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28560538/coenzyme-q10-and-niacin-mitigate-streptozotocin-induced-diabetic-encephalopathy-in-a-rat-model
#10
Tarek K Motawi, Hebatallah A Darwish, Manal A Hamed, Nagy S El-Rigal, Asmaa F Aboul Naser
Diabetic encephalopathy is an important complication of diabetes characterized by cognitive impairment, neurochemical and structural abnormalities. This study aimed to investigate the effect of coenzyme Q10 (CoQ10) and niacin as well as their combination in the treatment of encephalopathy associated with streptozotocin (STZ)- induced diabetes in rats. Glibenclamide (reference diabetic drug) and donepezil hydrochloride (acetylcholinesterase inhibitor) were also evaluated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg)...
May 30, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28521305/bushen-yizhi-formula-ameliorates-cognitive-dysfunction-through-sirt1-er-stress-pathway-in-samp8-mice
#11
Shi-Jie Zhang, Ting-Ting Xu, Lin Li, Yu-Min Xu, Zi-Ling Qu, Xin-Chen Wang, Shui-Qing Huang, Yi Luo, Na-Chuan Luo, Ping Lu, Ya-Fei Shi, Xin Yang, Qi Wang
The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514890/spatial-recognition-test-a-novel-cognition-task-for-assessing-topographical-memory-in-mice
#12
Enes Havolli, Mark Dw Hill, Annie Godley, Pascal Jd Goetghebeur
Dysfunction in topographical memory is a core feature of several neurological disorders. There is a large unmet medical need to address learning and memory deficits as a whole in central nervous system disease. There are considerable efforts to identify pro-cognitive compounds but current methods are either lengthy or labour intensive. Our test used a two chamber apparatus and is based on the preference of rodents to explore novel environments. It was used firstly to assess topographical memory in mice at different retention intervals (RI) and secondly to investigate the effect of three drugs reported to be beneficial for cognitive decline associated with Alzheimer's disease, namely: donepezil, memantine and levetiracetam...
June 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28499726/inhibitory-effect-of-donepezil-on-bradykinin-induced-increase-in-the-intracellular-calcium-concentration-in-cultured-cortical-astrocytes
#13
Kouki Makitani, Shota Nakagawa, Yasuhiko Izumi, Akinori Akaike, Toshiaki Kume
Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+)...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28495476/studies-on-diagnostic-biomarkers-and-therapeutic-mechanism-of-alzheimer-s-disease-through-metabolomics-and-hippocampal-proteomics
#14
Weiwei Lin, Jianmei Zhang, Yanmeng Liu, Ruijun Wu, Haisong Yang, Xiaobo Hu, Xiaomei Ling
Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and treatment are not sufficient so far. The purpose of this study is to develop biomarkers and therapeutic targets for diagnosis and better understanding of AD. As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF-MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD hippocampus by using label free nano-LC-MS/MS...
May 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28487125/design-synthesis-and-biological-evaluation-of-3-4-dihydro-2-1h-quinoline-o-alkylamine-derivatives-as-new-multipotent-cholinesterase-monoamine-oxidase-inhibitors-for-the-treatment-of-alzheimer-s-disease
#15
Zhipei Sang, Wanli Pan, Keren Wang, Qinge Ma, Lintao Yu, Wenmin Liu
A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives have been designed using a conjunctive approach that combines the JMC49 and donepezil. The most promising compound TM-33 showed potent and balance inhibitory activities toward ChE and MAO (eeAChE, eqBuChE, hMAO-A and hMAO-B with IC50 values of 0.56μM, 2.3μM, 0...
April 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28458525/rivastigmine-the-advantages-of-dual-inhibition-of-acetylcholinesterase-and-butyrylcholinesterase-and-its-role-in-subcortical-vascular-dementia-and-parkinson-s-disease-dementia
#16
REVIEW
Nagaendran Kandiah, Ming-Chyi Pai, Vorapun Senanarong, Irene Looi, Encarnita Ampil, Kyung Won Park, Ananda Krishna Karanam, Stephen Christopher
Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28458424/evaluation-of-neuroprotective-effect-of-quercetin-with-donepezil-in-scopolamine-induced-amnesia-in-rats
#17
Laxmi Adiveppa Pattanashetti, Ashok D Taranalli, Vinay Parvatrao, Rohit H Malabade, Dushyant Kumar
OBJECTIVE: The objective of this study was to evaluate the neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. MATERIALS AND METHODS: Five groups of adult male Wistar rats (12 months old) weighing 180-200 g (n = 6) were used. The normal control group received normal saline and test group animals were pretreated orally with quercetin (25 mg/kg), donepezil (3 mg/kg), and a combination of quercetin (25 mg/kg) with donepezil (3 mg/kg), respectively, dosed at every 24 h interval for 14 consecutive days, afterward amnesia was induced by scopolamine (3 mg/kg) on the 14(th) day through intraperitoneal route...
January 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28454848/design-synthesis-and-evaluation-of-multitarget-directed-ligands-against-alzheimer-s-disease-based-on-the-fusion-of-donepezil-and-curcumin
#18
Jun Yan, Jinhui Hu, Anqiu Liu, Lin He, Xingshu Li, Hui Wei
By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC50=187nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Aβ1-42 self-aggregation at 20μM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b-Cu(II) complex...
April 18, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28442406/anti-amnesic-effect-of-extract-and-alkaloid-fraction-from-aerial-parts-of-peganum-harmala-on-scopolamine-induced-memory-deficits-in-mice
#19
Wei Liu, Yudan Zhu, Yongli Wang, Shenglan Qi, Yuwen Wang, Chao Ma, Shuping Li, Bo Jiang, Xuemei Cheng, Zhengtao Wang, Zhenyu Xuan, Changhong Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches...
April 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28427041/the-efficacy-of-donepezil-administration-on-acetylcholinesterase-activity-and-altered-redox-homeostasis-in-alzheimer-s-disease
#20
Pinar Atukeren, Mahir Cengiz, Hakan Yavuzer, Remise Gelisgen, Esma Altunoglu, Sena Oner, Fusun Erdenen, Damla Yuceakın, Himmet Derici, Ufuk Cakatay, Hafize Uzun
Alzheimer's disease (AD) is a serious multifactorial disorder with progressive neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of the enzyme acetylcholinesterase (AChE), as one of the major therapeutic strategies, is considered to be offering only symptomatic relief and moderate disease modifying effect. We intended to investigate the effects of acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant-antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N-FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox homeostasis in Alzheimer patients also correlated with AChE activity...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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