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Huperzine

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https://www.readbyqxmd.com/read/28330463/global-transcriptome-analysis-of-huperzia-serrata-and-identification-of-critical-genes-involved-in-the-biosynthesis-of-huperzine-a
#1
Mengquan Yang, Wenjing You, Shiwen Wu, Zhen Fan, Baofu Xu, Mulan Zhu, Xuan Li, Youli Xiao
BACKGROUND: Huperzia serrata (H. serrata) is an economically important traditional Chinese herb with the notably medicinal value. As a representative member of the Lycopodiaceae family, the H. serrata produces various types of effectively bioactive lycopodium alkaloids, especially the huperzine A (HupA) which is a promising drug for Alzheimer's disease. Despite their medicinal importance, the public genomic and transcriptomic resources are very limited and the biosynthesis of HupA is largely unknown...
March 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28295437/a-novel-assay-to-determine-acetylcholinesterase-activity-the-application-potential-for-screening-of-drugs-against-alzheimer-s-disease
#2
Liang Peng, Zhengxing Rong, Hao Wang, Biyun Shao, Lei Kang, Hong Qi, Hongzhuan Chen
Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD) featured by ACh deficiency. However, the methods to precisely determine AChE activity are still under development. Here, we created a new method to exploit acetylcholine-d4 (ACh-d4 ) as a surrogate substrate of ACh and measure product choline-d4 (Ch-d4 ) via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically...
March 10, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28219697/effect-of-salvia-miltiorrhiza-root-extract-on-brain-acetylcholinesterase-and-butyrylcholinesterase-activities-their-mrna-levels-and-memory-evaluation-in-rats
#3
Marcin Ozarowski, Przemyslaw L Mikolajczak, Anna Piasecka, Radoslaw Kujawski, Joanna Bartkowiak-Wieczorek, Anna Bogacz, Michal Szulc, Ewa Kaminska, Malgorzata Kujawska, Agnieszka Gryszczynska, Piotr Kachlicki, Waldemar Buchwald, Andrzej Klejewski, Agnieszka Seremak-Mrozikiewicz
Salvia miltiorrhiza (Lamiaceae), one of the most important and popular plants of traditional medicine of Asia, is used for the prevention and treatment of cardiovascular diseases and in central nervous system disturbances. The main aim of this study was to assess the influence of subchronic (28-fold) administration of Salvia miltiorrhiza root extract (SE, 200mg/kg, p.o.) on behavioural activity and memory of rats and to evaluate the activities of cholinesterases (AChE and BuChE) and gene expression levels of AChE and BuChE as well as of beta-secretase (BACE1) in the hippocampus and frontal cortex in vivo...
May 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28125507/behavioural-effects-of-novel-multitarget-anticholinesterasic-derivatives-in-alzheimer-s-disease
#4
Lydia Giménez-Llort, Miriam Ratia, Belén Pérez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, M Victoria Clos
The current pharmacological approach to Alzheimer's disease (AD) treatment, mostly based on acetylcholinesterase inhibitors (AChEIs), is being revisited, especially in terms of the temporal frames and the potential benefits of their noncanonic actions, raising the question of whether inhibitors of AChE might also act in a disease-modifying manner. Besides, in the last decades, the pharmacophoric moieties of known AChEIs have been covalently linked to other pharmacophores in the pursuit of multitarget hybrid molecules that are expected to induce long-lasting amelioration of impaired neurotransmission and clinical symptoms but also to exert disease-modifying effects...
April 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28111749/progress-report-on-new-antiepileptic-drugs-a-summary-of-the-thirteenth-eilat-conference-on-new-antiepileptic-drugs-and-devices-eilat-xiii
#5
REVIEW
Meir Bialer, Svein I Johannessen, René H Levy, Emilio Perucca, Torbjörn Tomson, H Steve White
The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689)...
January 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28110700/huperzine-a-a-promising-anticonvulsant-disease-modifying-and-memory-enhancing-treatment-option-in-alzheimer-s-disease
#6
Ugur Damar, Roman Gersner, Joshua T Johnstone, Steven Schachter, Alexander Rotenberg
Alzheimer's disease (AD) is the most frequent cause of dementia. Besides cognitive deterioration, patients with AD are prone to seizures - more than 20% of patients diagnosed with AD experience at least one unprovoked seizure and up to 7% have recurrent seizures. Although available antiepileptic drugs (AEDs) may suppress seizures in patients with AD, they may also worsen cognitive dysfunction and increase the risk of falls. On the basis of preclinical studies, we hypothesize that Huperzine A (HupA), a safe and potent acetylcholinesterase (AChE) inhibitor with potentially disease-modifying qualities in AD, may have a realistic role as an anticonvulsant in AD...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28089246/identification-and-characterization-of-l-lysine-decarboxylase-from-huperzia-serrata-and-its-role-in-the-metabolic-pathway-of-lycopodium-alkaloid
#7
Baofu Xu, Lei Lei, Xiaocen Zhu, Yiqing Zhou, Youli Xiao
Lysine decarboxylation is the first biosynthetic step of Huperzine A (HupA). Six cDNAs encoding lysine decarboxylases (LDCs) were cloned from Huperzia serrata by degenerate PCR and rapid amplification of cDNA ends (RACE). One HsLDC isoform was functionally characterized as lysine decarboxylase. The HsLDC exhibited greatest catalytic efficiency (kcat/Km, 2.11 s(-1) mM(-1)) toward L-lysine in vitro among all reported plant-LDCs. Moreover, transient expression of the HsLDC in tobacco leaves specifically increased cadaverine content from zero to 0...
April 2017: Phytochemistry
https://www.readbyqxmd.com/read/27900576/time-course-behavioral-safety-and-protective-efficacy-of-centrally-active-reversible-acetylcholinesterase-inhibitors-in-cynomolgus-macaques
#8
Lindsey R Hamilton, Steven C Schachter, Todd M Myers
Galantamine hydrobromide and (-)huperzine A, centrally active reversible acetylcholinesterase inhibitors, are potentially superior to the current standard, pyridostigmine bromide, as a pretreatment for organophosphorus chemical warfare nerve agent intoxication. Galantamine, huperzine, and pyridostigmine were compared for time course of acetylcholinesterase inhibition in 12 cynomolgus macaques. Although both galantamine and huperzine shared a similar time course profile for acetylcholinesterase inhibition, huperzine was 88 times more potent than galantamine...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27848250/pharmacological-effects-of-active-components-of-chinese-herbal-medicine-in-the-treatment-of-alzheimer-s-disease-a-review
#9
REVIEW
Zhi-Yong Wang, Jian-Gang Liu, Hao Li, Hui-Ming Yang
Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM)...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27829351/recent-updates-in-imperative-natural-compounds-for-healthy-brain-and-nerve-function-a-systematic-review-of-implications-for-multiple-sclerosis
#10
Nima Sanadgol, Shahram Shahraki Zahedani, Mohammad Sharifzadeh, Roghayeh Khalseh, Gullam Reza Barbari, Mohammad Abdollahi
BACKGROUND: The evolution of the 'Green' movement in western society has changed attitudes in the general population who now perceive natural compounds as being inherently harmless and more desirable than artificial chemical products. OBJECTIVE: Considering the growing interest towards introducing naturally emerged medicines, the purpose of this review was to overview the ongoing research into prevention and treatment of multiple sclerosis (MS) lesions. METHOD: This review was carried out by searching bibliographic databases such as PubMed and Scopus for studies reported between 1th January 2008 to 30rd January 2016 on MS patients or animal models of MS, investigating the beneficial effects of natural compounds in MS treatment...
November 8, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27799911/huperzine-a-provides-robust-and-sustained-protection-against-induced-seizures-in-scn1a-mutant-mice
#11
Jennifer C Wong, Stacey B B Dutton, Stephen D Collins, Steven Schachter, Andrew Escayg
De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15-20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27774814/recent-progress-in-repositioning-alzheimer-s-disease-drugs-based-on-a-multitarget-strategy
#12
M Amélia Santos, Karam Chand, Sílvia Chaves
Alzheimer's disease (AD) is a serious progressive neurological disorder, characterized by impaired cognition and profound irreversible memory loss. The multifactorial nature of AD and the absence of a cure so far have stimulated medicinal chemists worldwide to follow multitarget drug-design strategies based on repositioning approved drugs. This review describes a summary of recently published works focused on tailoring new derivatives of US FDA-approved acetylcholinesterase inhibitors, in addition to huperzine (a drug approved in China), either by hybridization with other pharmacophore elements (to hit more AD targets), or by combination of two FDA-approved drugs...
October 24, 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27751854/evaluation-of-the-in%C3%A2-vitro-and-in%C3%A2-vivo-metabolic-pathway-and-cytochrome-p450-inhibition-induction-profile-of-huperzine-a
#13
Ping-Ping Lin, Xue-Ning Li, Fei Yuan, Wei-Li Chen, Meng-Jie Yang, Hong-Rong Xu
Huperzine A (HupA), one of the reversible and selective acetylcholinesterase inhibitors derived from Chinese herb Huperzia Serrata, possesses affirmative action of ameliorating cognitive dysfunction of Alzheimer's disease. Up to now, the effects of HupA on human cytochrome P450s (CYPs) have not been fully elucidated. The purpose of the present study was to clarify the metabolic pathway of HupA in vitro and in vivo, and to evaluate the CYPs inhibition/induction profile of HupA in vitro. The catalytic activity of CYP enzymes (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4) was measured by the quantification of specific enzyme substrates using validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods...
November 11, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27725508/chemical-transformation-of-an-intermediate-in-the-synthesis-of-huperzine-a-leading-to-a-diverse-array-of-molecules
#14
Satoshi Yokoshima, Masatsugu Ishikawa, Youko Beniyama, Tohru Fukuyama
Chemical transformation of an early intermediate in our synthesis of huperzine A provided a diverse array of molecules in which a variety of functional groups could be embedded.
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27712576/multiple-targets-for-management-of-alzheimer-s-disease-a-review
#15
Sayeed Ahmad, Salman Akhtar, Qazi Mohammad Sajid Jamal, Syed Mohd Danish Rizvi, Mohammad A Kamal, M Kalim A Khan, Mohd Haris Siddiqui
AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior...
October 3, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27659301/anti-ageing-active-ingredients-from-herbs-and-nutraceuticals-used-in-traditional-chinese-medicine-pharmacological-mechanisms-and-implications-for-drug-discovery
#16
REVIEW
Chun-Yan Shen, Jian-Guo Jiang, Li Yang, Da-Wei Wang, Wei Zhu
Ageing, an unanswered question in the medical field, is a multifactorial process that results in a progressive functional decline in cells, tissues and organisms. Although it is impossible to prevent ageing, slowing down the rate of ageing is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life and its role in anti-ageing is getting more and more attention. This article summarizes the work done on the natural products from TCM that are reported to have anti-ageing effects, in the past two decades...
September 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27642355/primary-investigation-for-the-mechanism-of-biatractylolide-from-atractylodis-macrocephalae-rhizoma-as-an-acetylcholinesterase-inhibitor
#17
Yong-Chao Xie, Ning Ning, Li Zhu, Dan-Ning Li, Xing Feng, Xiao-Ping Yang
Biatractylolide was isolated from ethyl acetate extract of dried Atractylodis Macrocephalae Rhizoma root by multistep chromatographic processing. Structure of biatractylolide was confirmed by (1)H-NMR and (13)C-NMR. The IC50 on acetylcholinesterase (AChE) activity was 6.5458 μg/mL when the control IC50 value of huperzine A was 0.0192 μg/mL. Molecular Docking Software (MOE) was used to discover molecular sites of action between biatractylolide and AChE protein by regular molecular docking approaches. Moreover, biatractylolide downregulated the expression of AChE of MEF and 293T cells in a dose-dependent manner...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27605862/huperzine-a-for-treatment-of-cognitive-impairment-in-major-depressive-disorder-a-systematic-review-of-randomized-controlled-trials
#18
REVIEW
Wei Zheng, Ying-Qiang Xiang, Gabor S Ungvari, F K Helen Chiu, Chee H Ng, Ying Wang, Yu-Tao Xiang
BACKGROUND: Acetylcholinesterase (AChE) inhibitors have been shown to be effective in treating cognitive impairment in animal models and in human subjects with major depressive disorder (MDD). Huperzine A (HupA), a Traditional Chinese Medicine derived from a genus of clubmosses known as Huperzineserrata, is a powerful AChE inhibitor that has been used as an adjunctive treatment for MDD, but no meta-analysis on HupA augmentation for MDD has yet been reported. AIM: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTS) about HupA augmentation in the treatment of MDD to evaluate its efficacy and safety...
April 25, 2016: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/27554967/effect-of-huperzine-a-on-a%C3%AE-induced-p65-of-astrocyte-in-vitro
#19
Lushuang Xie, Cen Jiang, Zhang Wang, Xiaohong Yi, Yuanyuan Gong, Yunhui Chen, Yan Fu
Alzheimer's disease (AD) is the most common cause of dementia. Its pathology often accompanies inflammatory action, and astrocytes play important roles in such procedure. Rela(p65) is one of significant message factors in NF-κB pathway which has been reported high expression in astrocyte treated by Aβ. HupA, an alkaloid isolated from Chinese herb Huperzia serrata, has been widely used to treat AD and observations reflected that it improves memory and cognitive capacity of AD patients. To reveal its molecular mechanisms on p65, we cultured astrocytes, built Aβ-induced AD model, treated astrocytes with HupA at different concentrations, assayed cell viability with MTT, and detected p65 expression by immunohistochemistry and PCR...
December 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27535978/acetylcholinesterase-inhibitors-for-alzheimer-s-disease-treatment-ameliorate-acetaminophen-induced-liver-injury-in-mice-via-central-cholinergic-system-regulation
#20
Jianqiao Zhang, Leiming Zhang, Xue Sun, Yanting Yang, Liang Kong, Chengwen Lu, Guangyao Lv, Tian Wang, Hongbo Wang, Fenghua Fu
Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic α7 nicotine acetylcholine receptor (α7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0...
November 2016: Journal of Pharmacology and Experimental Therapeutics
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