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Tianxiang Lei, Huan Wang, Songling Li, Jianwei Shen, Shilong Chen, Xiaojian Cai, Dangwei Zhou
To achieve a high yield of tropane alkaloids (TA) and exploit the alpine plant sustainably, an optimized protocol for induction and establishment of hairy roots culture of Prezwalskia tangutica Maxim was developed through selection of appropriate Agrobacterium strain and the explant type. The hypocotyl is more readily facile to induce the HR than the cotyledon is when infected with the three different agrobacterium strains. MUS440 has an efficiency (of up to 20%), whereas the ATCC10060 (A4) can induce HR on both types of explants with the highest frequency (33...
March 2018: 3 Biotech
Yue Wei, Cui-Ping Zhang, Shuang Guo, Ke-Huan Lu, Xing Liu, Yi Yang, Zhi-Hua Liao, Neng-Biao Wu
Hyoscyamine and scopolamine are two main alkaloids in Atropa belladonna with great medicinal value. In this paper, the contents of hyoscyamine and scopolamine, the upstream products in alkaloid synthesis, and the expression levels of key enzyme genes PMT, TRⅠ and H6H in secondary metabolism of A. belladonna seedlings were measured to clarify the mechanism of nitrogen forms regulating alkaloids synthesis.The results showed that the 50/50 (NH⁺₄/NO⁻₃) treatment was more favorable for the accumulation of alkaloids and the conversion of hyoscyamine to scopolamine...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Md Moniruzzaman, Young-Won Chin, Jungsook Cho
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells...
March 15, 2018: Cell Stress & Chaperones
Xue-Yang Jiang, Ting-Kai Chen, Jun-Ting Zhou, Si-Yu He, Hong-Yu Yang, Yao Chen, Wei Qu, Feng Feng, Hao-Peng Sun
Designing multitarget-directed ligands (MTDLs) is considered to be a promising approach to address complex and multifactorial maladies such as Alzheimer's disease (AD). The concurrent inhibition of the two crucial AD targets, glycogen synthase kinase-3β (GSK-3β) and human acetylcholinesterase ( h AChE), might represent a breakthrough in the quest for clinical efficacy. Thus, a novel family of GSK-3β/AChE dual-target inhibitors was designed and synthesized. Among these hybrids, 2f showed the most promising profile as a nanomolar inhibitor on both h AChE (IC50 = 6...
March 8, 2018: ACS Medicinal Chemistry Letters
Li-Min Mao, Hunter J Faris, John Q Wang
The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. SFK members, Src and especially Fyn, are expressed in the striatum. These SFK members are involved in the regulation of neuronal and synaptic activities and are linked to the pathogenesis of a variety of neuropsychiatric and neurodegenerative disorders. Given the fact that muscarinic acetylcholine (mACh) receptors are highly expressed in striatal neurons and are critical for the regulation of striatal function, we investigated the role of mACh receptors in the regulation of SFKs in the adult rat striatum in vivo...
March 12, 2018: Journal of Molecular Neuroscience: MN
Allie J Widman, Lori L McMahon
Low-dose ketamine, an open-channel N -methyl d-aspartate receptor (NMDAR) antagonist, mediates rapid antidepressant effects in humans that are mimicked in preclinical rodent models. Disinhibition of pyramidal cells via decreased output of fast-spiking GABAergic interneurons has been proposed as a key mechanism that triggers the antidepressant response. Unfortunately, to date, disinhibition has not been directly demonstrated. Furthermore, whether disinhibition is a common mechanism shared among other antagonists with rapid antidepressant properties in humans has not been investigated...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Neeraj K Sethiya, Alok Nahata, Pawan Kumar Singh, S H Mishra
OBJECTIVE: The present study was undertaken to evaluate the neuropharmacological effect of four herbs commonly identified as source of Shankhpushpi. BACKGROUND: Shankhpushpi is an Ayurvedic drug, widely used for its actions on the central nervous system, especially to improve intellect and boost memory. Four botanicals viz. Canscora decussata Schult. (CD), Clitorea ternatea Linn. (CT), Convolvulus pluricaulis Choisy. (CP) and Evolvulus alsinoides Linn. (EA) are considered as sources of Shankhpushpi by Indian practitioners on the basis of their morphological descriptions given in ancient texts...
March 9, 2018: Journal of Ayurveda and Integrative Medicine
Devendra Kumar, Sukesh K Gupta, Ankit Ganeshpurkar, Gopichand Gutti, Sairam Krishnamurthy, Gyan Modi, Sushil K Singh
Novel multifunctional 3,6-Diphenyl-1,4-bis(phenylsulfonyl)piperazine-2,5-dione derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). The designed scaffold has blood brain barrier penetrating ability, acetylcholinesterase (AChE) and matrix metalloproteinase-2 (MMP-2) inhibition potential. Compounds 52 and 46 showed very significant inhibition against AChE, IC50  = 32.45 ± 0.044, 28.65 ± 0.029, BuChE, IC50  = 157.95 ± 0.264, 160.58 ± 0.082 and MMP-2, IC50  = 36...
February 27, 2018: European Journal of Medicinal Chemistry
J F Golding, K A Wesnes, B R Leaker
AIMS: The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist Darifenacin, oral Hyoscine hydrobromide and Placebo on motion sickness induced by cross-coupled stimulation. METHODS: The effects of Darifenacin 10 mg or 20 mg, Hyoscine hydrobromide 0.6 mg and Placebo were assessed in a randomised, double-blind, 4-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated...
March 9, 2018: British Journal of Clinical Pharmacology
Panos Zanos, Scott M Thompson, Ronald S Duman, Carlos A Zarate, Todd D Gould
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites...
March 7, 2018: CNS Drugs
Meng Li, Yu Zhao, Li Zhou, Jia Yu, Jian Wang, Xingjie Guo
In this work, the enantiomeric separation of ten anticholinergic drugs was first examined on two derivative polysaccharide chiral stationary phases (CSPs), i.e., Chiralpak ID and Chiralpak IA in the normal phase mode. Except for scopolamine hydrobromide, the remaining nine analytes could be completely separated with good resolutions using both columns under the optimized mobile phase conditions. And the enantiomeric discrimination ability of the studied CSPs towards nine analytes was in the order of Chiralpak ID > Chiralpak IA...
March 7, 2018: Electrophoresis
Yong-Hyun Ko, Sun Yeou Kim, Seok-Yong Lee, Choon-Gon Jang
Daidzein is one of the major isoflavones found in soy food and plants. Following ingestion, daidzein is readily converted to hydroxylated metabolites in the human body. 6,7,4'-Trihydroxyisoflavone (THIF), one of the metabolites of daidzein, has several pharmacological activities, including anti-cancer and anti-obesity properties. However, no reports exist on the effects of 6,7,4'-THIF for cognitive function in mice. The present study aimed to investigate the effects of 6,7,4'-THIF against scopolamine-induced learning and memory impairments using the Y-maze and passive avoidance test...
March 3, 2018: European Journal of Pharmacology
Hye-Lim Lee, Sung-Ah Lim, Hye-Won Lee, Ho-Ryong Yoo, Hyeong-Geug Kim
We evaluated neuropharmacological properties of Yuk-Mi-Jihwang-Tang (YJT) against scopolamine injection-induced memory impairment mice model. Mice were orally administered with YJT (50, 100, or 200 mg/kg) or tacrine (TAC, 12.5 mg/kg) for 10 days. At the first day of Morris water maze task, scopolamine (2 mg/kg) was intraperitoneally injected before 30 min of it. The hippocampal memory function was determined by the Morris water maze task for 5 days consecutively. Scopolamine drastically increased escape latency and decreased time spent in target quadrant...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Md Mohibbullah, Jae-Suk Choi, Mohammad Maqueshudul Haque Bhuiyan, Md Nazmul Haque, Md Khalilur Rahman, Il Soo Moon, Yong-Ki Hong
Exogenous neurotrophins can induce neuronal differentiation, outgrowth, survival, and synaptic function in the central nervous system. In primary cultures of rat hippocampal neurons, an ethanol extract of the red alga Gracilariopsis chorda (GCE) and its active compound arachidonic acid (AA) significantly increased the densities of dendritic filopodia and spines, promoted the expression of presynaptic vesicle protein 2 (SV2) and postsynaptic density protein 95 (PSD-95), induced robust synaptogenesis, and increased the expression of cell division control protein 42 (CDC42) and actin-related protein 2 (ARP2), which are important for actin organization in dendritic protrusions, and facilitated presynaptic plasticity by increasing the size of the synaptic vesicle pool at presynaptic nerve terminals...
March 2, 2018: Journal of Medicinal Food
Sweta Srivas, Mahendra K Thakur
Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity...
March 1, 2018: Journal of Neurochemistry
Gaofeng Sheng, Jinlin Zhang, Shengfeng Gao, Yuanyuan Gu, Bo Jiang, Qiufang Gao
Patients with Alzheimer's disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task...
2018: Biological & Pharmaceutical Bulletin
Bai Hui Chen, Joon Ha Park, Tae-Kyeong Lee, Minah Song, Hyunjung Kim, Jae Chul Lee, Young-Myeong Kim, Choong-Hyun Lee, In Koo Hwang, Il Jun Kang, Bing Chun Yan, Moo-Ho Won, Ji Hyeon Ahn
Animal models of scopolamine-induced amnesia are widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies have identified that melatonin improves cognitive dysfunction in animal models. In this study, using a mouse model of scopolamine-induced amnesia, we assessed spatial and short-term memory functions for 4 weeks, investigated the expression of myelin-basic protein (MBP) in the dentate gyrus, and examined whether melatonin and scopolamine cotreatment could keep cognitive function and MBP expression...
February 21, 2018: Chemico-biological Interactions
Xin Lu, Si-Yu He, Qi Li, Hongyu Yang, Xueyang Jiang, Hongzhi Lin, Yao Chen, Wei Qu, Feng Feng, Yaoyao Bian, You Zhou, Haopeng Sun
In our endeavor towards the development of potent multi-target ligands for the treatment of Alzheimer's disease, miconazole was identified to show BuChE-IDO1 dual-target inhibitory effects. Morris water maze test indicated that miconazole obviously ameliorated the cognitive function impaired by scopolamine. Furthermore, it showed good safety in primary hepatotoxicity evaluation. Based on these results, we designed, synthesized, and evaluated a series of miconazole derivatives as BuChE-IDO1 dual-target inhibitors...
February 13, 2018: Bioorganic & Medicinal Chemistry
Cong Lu, Jingwei Lv, Liming Dong, Ning Jiang, Yan Wang, Qiong Wang, Yinghui Li, Shanguang Chen, Bei Fan, Fengzhong Wang, Xinmin Liu
20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment...
February 22, 2018: Phytotherapy Research: PTR
Chang Yell Shin, Hae-Sun Kim, Kwang-Ho Cha, Dong Han Won, Ji-Yun Lee, Sun Woo Jang, Uy Dong Sohn
A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.2 ± 0.4 h and 1...
February 21, 2018: Biomolecules & Therapeutics
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