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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...
October 14, 2016: Biochemical and Biophysical Research Communications
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
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
Chun-Yan Shen, Jian-Guo Jiang, Li Yang, Da-Wei Wang, Wei Zhu
Aging, a puzzling question in the medical field, is a multifactorial process that results in a progressive functional decline at cellular, tissue, and organismal levels. Although it is impossible to prevent aging, slowing down the pace of aging is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life, its role in anti-aging is getting more and more attention. This article summarizes the natural products from TCM that are reported to have anti-aging effects in the past two decades...
September 23, 2016: British Journal of Pharmacology
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
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
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
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
Ling-Xue Tao, Xiao-Tian Huang, Yu-Ting Chen, Xi-Can Tang, Hai-Yan Zhang
AIM: Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. METHODS: Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays...
August 8, 2016: Acta Pharmacologica Sinica
Huilin Yang, Silu Peng, Zhibin Zhang, Riming Yan, Ya Wang, Jixun Zhan, Du Zhu
Huperzine A (HupA) is a drug used for the treatment of Alzheimer's disease. However, the biosynthesis of this medicinally important compound is not well understood. The HupA biosynthetic pathway is thought to be initiated by the decarboxylation of lysine to form cadaverine, which is then converted to 5-aminopentanal by copper amine oxidase (CAO). In this study, we cloned and expressed an SsCAO gene from a HupA-producing endophytic fungus, Shiraia sp. Slf14. Analysis of the deduced protein amino acid sequence showed that it contained the Asp catalytic base, conserved motif Asn-Tyr-Asp/Glu, and three copper-binding histidines...
December 2016: Protein Expression and Purification
Javier Urra, Jan Blohberger, Michelle Tiszavari, Artur Mayerhofer, Hernan E Lara
Growth and differentiation of ovarian follicles are regulated by systemic and local factors, which may include acetylcholine (ACh). Granulosa cells (GCs) of growing follicles and luteal cells produce ACh and in cultured GCs it exerts trophic actions via muscarinic receptors. However, such actions were not studied in vivo. After having established that rat ovarian GCs and luteal cells express the ACh-metabolizing enzyme ACh esterase (AChE), we examined the consequences of local application of an AChE inhibitor, huperzine A (HupA), by osmotic minipump delivery into the ovarian bursa of hemiovariectomized rats...
2016: Scientific Reports
Sen-Zhi Zhu, Wei-Ping Huang, Lin-Qiang Huang, Yong-Li Han, Qian-Peng Han, Gao-Feng Zhu, Miao-Yun Wen, Yi-Yu Deng, Hong-Ke Zeng
Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats...
September 19, 2016: Neuroscience Letters
Jing-Han Feng, Bao-Chang Cai, Wei-Feng Guo, Ming-Yan Wang, Yong Ma, Qiao-Xi Lu
OBJECTIVE: To explore the protective effects of Tongmai Yizhi Decoction (, TYD), a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1-40 (Aβ1-40) peptide and ibotenic (IBO)-induced Alzheimer's disease (AD) model rats. METHODS: The in vivo model was established by injecting Aβ1-40 and IBO into left hippocampal CA1 area of Sprague-Dawley (SD) rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19...
July 9, 2016: Chinese Journal of Integrative Medicine
Wei Zheng, Ying-Qiang Xiang, Xian-Bin Li, Gabor S Ungvari, Helen F K Chiu, Feng Sun, Carl D'Arcy, Xiangfei Meng, Yu-Tao Xiang
OBJECTIVE: The aim of this study was to examine the efficacy of huperzine A (HupA), an isolate of Huperzine serrata, in the treatment of cognitive deficits in schizophrenia spectrum disorders. METHODS: PubMed, PsycINFO, Embase, Cochrane Library, Cochrane Controlled Trials Register, WanFang, Chinese Biomedical, and China Journal Net databases were searched from inception to 15 July 2015 for randomized controlled trials (RCTs) in English or Chinese of HupA augmentation of antipsychotic drug therapy versus placebo or ongoing antipsychotic treatment...
July 2016: Human Psychopharmacology
Marcin Ozarowski, Przemyslaw L Mikolajczak, Anna Piasecka, Piotr Kachlicki, Radoslaw Kujawski, Anna Bogacz, Joanna Bartkowiak-Wieczorek, Michal Szulc, Ewa Kaminska, Malgorzata Kujawska, Jadwiga Jodynis-Liebert, Agnieszka Gryszczynska, Bogna Opala, Zdzislaw Lowicki, Agnieszka Seremak-Mrozikiewicz, Boguslaw Czerny
Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Lei Sheng, Yi Qu, Jing Yan, Gang-Yi Liu, Wei-Liang Wang, Yi-Jun Wang, Hong-Yi Wang, Meng-Qi Zhang, Chuan Lu, Yun Liu, Jing-Yin Jia, Chao-Ying Hu, Xue-Ning Li, Chen Yu, Hong-Rong Xu
AIM: Our preliminary results show that huperzine A, an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD) patients in China, exhibits different pharmacokinetic features in elderly and young healthy subjects. However, its pharmacokinetic data in elderly subjects remains unavailable to date. Thus, we developed a population pharmacokinetic (PPK) model of huperzine A in elderly Chinese people, and identified the covariate affecting its pharmacokinetics for optimal individual administration...
July 2016: Acta Pharmacologica Sinica
Kate Laver, Suzanne Dyer, Craig Whitehead, Lindy Clemson, Maria Crotty
OBJECTIVE: To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia. DESIGN: Overview of systematic reviews. METHODS: A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included...
2016: BMJ Open
Chun-Xia Ban, Shi-Fu Xiao, Xiang Lin, Tao Wang, Qi Qiu, Min-Jie Zhu, Xia Li
BACKGROUND: China has more cases of Alzheimer's disease (AD) than any other country in the world. As training to recognize and manage dementia is in its early stage, it is important to study clinicians' current prescription preferences for treating patients with AD. METHODS: This study surveyed neurologists, psychiatrists, and general physicians (GPs) in Shanghai who had outpatients with AD, using a questionnaire asking about their prescription preferences for these patients...
2016: Translational Neurodegeneration
Judith Peters, Nicolas Martinez, Marie Trovaslet, Kévin Scannapieco, Michael Marek Koza, Patrick Masson, Florian Nachon
We investigated the effects of non-covalent reversible and covalent irreversible inhibitors on human acetylcholinesterase and human butyrylcholinesterase. Remarkably a non-covalent inhibitor, Huperzine A, has almost no effect on the molecular dynamics of the protein, whereas the covalently binding nerve agent soman renders the molecular structure stiffer in its aged form. The modified movements were studied by incoherent neutron scattering on different time scales and they indicate a stabilization and stiffening of aged human acetylcholinesterase...
May 14, 2016: Physical Chemistry Chemical Physics: PCCP
U Damar, R Gersner, J T Johnstone, S Schachter, A Rotenberg
Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies...
June 2016: Expert Review of Neurotherapeutics
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