Neuroprotective effects of huperzine A: New therapeutic targets for neurodegenerative disease
Abstract
In recent years, the most common pharmacological treatment for Alzheimer's disease (AD) has been acetylcholinesterase (AChE) inhibition. However, this single-target approach has limited effectiveness and there is evidence that a multitarget approach might be more effective. Huperzine A (HupA), a novel alkaloid isolated from a Chinese herb, has neuroprotective effects that go beyond the inhibition of AChE. Recent data have demonstrated that HupA can ameliorate the learning and memory deficiency in animal models and AD patients. Its potentially beneficial actions include modification of beta-amyloid peptide processing, reduction of oxidative stress, neuronal protection against apoptosis, and regulation of the expression and secretion of nerve growth factor (NGF) and NGF signaling.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Huperzine-A lessens glutamate-induced cytotoxicity by antagonizing cerebral NMDA receptors.
“Huperzine-A has been proved to lessen the glutamate-induced cytotoxicity by its antagonizing action on cerebral N-methyl-D-aspartate (NMDA) receptors”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [137]
Cites
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
Hydrogen peroxide mediates amyloid β protein toxicity
Behl, C. (1994) · Cell · doi:10.1016/0092-8674(94)90131-7 · Cited by 2,074 · see citing works
Perry, E., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P., & Perry, R. H. (1978) · British medical journal · doi:10.1136/bmj.2.6150.1457 · Cited by 2,043 · see citing works
Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state
Pike, C., Burdick, D., Walencewicz, A., Glabe, C., & Cotman, C. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-04-01676.1993 · Cited by 1,417 · see citing works
Cleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., & Ward, P. J. (1990) · Science · doi:10.1126/science.2111583 · Cited by 1,403 · see citing works
Amyloid, the presenilins and Alzheimer’s disease
Hardy, J. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01030-2 · Cited by 1,370 · see citing works
Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A., & Butterfield, D. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3270 · Cited by 1,086 · see citing works
The mitochondrion in apoptosis: how Pandora's box opens
Zamzami, N., & Kroemer, G. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35048073 · Cited by 1,029 · see citing works
Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.
Loo, D. T., Copani, A., Pike, C. J., Whittemore, E. R., Walencewicz, A. J., & Cotman, C. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7951 · Cited by 1,022 · see citing works
Nitsch, R. M., Slack, B. E., Wurtman, R. J., & Growdon, J. H. (1992) · Science · doi:10.1126/science.1411529 · Cited by 898 · see citing works
Alzheimer's Disease--Genotypes, Phenotype, and Treatments
Selkoe, D. J. (1997) · Science · doi:10.1126/science.275.5300.630 · Cited by 871 · see citing works
Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide
Haass, C., & Selkoe, D. J. (1993) · Cell · doi:10.1016/0092-8674(93)90312-e · Cited by 833 · see citing works
Mattson, M. P., Cheng, B., Culwell, A. R., Esch, F. S., Lieberburg, I. M., & Rydel, R. E. (1993) · Neuron · doi:10.1016/0896-6273(93)90315-i · Cited by 795 · see citing works
Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04183.2001 · Cited by 777 · see citing works
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1985) · Science · doi:10.1126/science.2999977 · Cited by 549 · see citing works
Decker, M. W., & McGaugh, J. L. (1991) · Synapse · doi:10.1002/syn.890070209 · Cited by 524 · see citing works
Apoptosis driven by IP3‐linked mitochondrial calcium signals
Szalai, G., Krishnamurthy, R., & Hajnóczky, G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.22.6349 · Cited by 495 · see citing works
Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1
WANG, R., YAN, H., & TANG, X.-C. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00255.x · Cited by 470 · see citing works
Diffuse transmission by acetylcholine in the CNS
Descarries, L., Gisiger, V., & Steriade, M. (1997) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00050-6 · Cited by 406 · see citing works
Small, D. H., Nurcombe, V., Reed, G., Clarris, H. J., Moir, R. D., Beyreuther, K. T., & Masters, C. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02117.1994 · Cited by 389 · see citing works
Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders
Youdim, M. B. H., & Buccafusco, J. J. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.11.007 · Cited by 382 · see citing works
Samochocki, M., Höffle‐Maas, A., Fehrenbacher, A., Jostock, R., Ludwig, J., Christner, C., Radina, M., Zerlin, M., Ullmer, C., Pereira, E. F. R., et al. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.045773 · Cited by 345 · see citing works
Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42
LIU, R., Barkhordarian, H., Emadi, S., PARK, C., & Sierks, M. R. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.003 · Cited by 340 · see citing works
Danysz, W., Parsons, C. G., Möbius, H. J., Stöffler, A., & Quack, G. (2000) · Neurotoxicity Research · doi:10.1007/bf03033787 · Cited by 262 · see citing works
Trophic effect of β-amyloid precursor protein on cerebral cortical neurons in culture
Araki, W., Kitaguchi, N., Tokushima, Y., Ishii, K., Aratake, H., Shimohama, S., Nakamura, S., & Kimura, J. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)81412-3 · Cited by 213 · see citing works
Yu, S. P., Farhangrazi, Z. S., Ying, H. S.-C., Yeh, C.-H., & Choi, D. W. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0186 · Cited by 189 · see citing works
Xiao, X., Zhang, H., & Tang, X. C. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.10075 · Cited by 153 · see citing works
Anderson, A. J., Pike, C. J., & Cotman, C. W. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65041487.x · Cited by 134 · see citing works
Schubert, D. A., & Behl, C. (1993) · Brain Research · doi:10.1016/0006-8993(93)91331-l · Cited by 131 · see citing works
Wang, R., Zhang, H., & Tang, X. C. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01030-5 · Cited by 131 · see citing works
Wenk, G. L., Parsons, C. G., & Danysz, W. (2006) · Behavioural Pharmacology · doi:10.1097/00008877-200609000-00007 · Cited by 128 · see citing works
Jackson, T., Blader, I. J., Hammonds-Odie, L. P., Burga, C. R., Cooke, F. T., Hawkins, P. T., Wolf, A. G., Heldman, K. A., & Theibert, A. B. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.2.289 · Cited by 125 · see citing works
Maelicke, A., Schrattenholz, A. S., Samochocki, M., Radina, M., & Albuquerque, E. X. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00214-x · Cited by 123 · see citing works
Cai, J. X., Ma, Y.-Y., Xu, L., & Hu, X.-T. (1993) · Brain Research · doi:10.1016/0006-8993(93)91034-p · Cited by 122 · see citing works
Haring, R., Fisher, A., Marciano, D., Pittel, Z., Kloog, Y., Zuckerman, A., Eshhar, N., & Heldman, E. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71052094.x · Cited by 122 · see citing works
Ved, H. S., Koenig, M. L., Dave, J. R., & Doctor, B. P. (1997) · Neuroreport · doi:10.1097/00001756-199703030-00029 · Cited by 116 · see citing works
Alzheimer?s disease and NGF signaling
Salehi, A., Delcroix, J., & Swaab, D. F. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0091-x · Cited by 112 · see citing works
Huperzine A and tacrine attenuate ?-amyloid peptide-induced oxidative injury
Xiao, X., Wang, R., & Tang, X. C. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000901)61:5 · Cited by 101 · see citing works
The NMDA receptor ion channel: a site for binding of huperzine A
Gordon, R. K., Nigam, S. V., Weitz, J. A., Dave, J. R., Doctor, B. P., & Ved, H. S. (2001) · Journal of Applied Toxicology · doi:10.1002/jat.805 · Cited by 100 · see citing works
Role of neurotransmission in the regulation of amyloid β-protein precursor processing
Nitsch, R. M., & Growdon, J. H. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90325-5 · Cited by 98 · see citing works
Huperzine A protects rat pheochromocytoma cells against hydrogen peroxide-induced injury
Xiao, X., Yang, J., & Tang, X. C. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00695-3 · Cited by 90 · see citing works
Wang, Z., Tang, L., Yan, H., Wang, Y., & Tang, X. C. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.03.027 · Cited by 90 · see citing works
The Adhesion Function on Acetylcholinesterase Is Located at the Peripheral Anionic Site
Johnson, G., & Moore, S. W. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0705 · Cited by 87 · see citing works
Morimoto, T., Ohsawa, I., Takamura, C., Ishiguro, M., & Kohsaka, S. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980115)51:2 · Cited by 85 · see citing works
Xiao, X., Wang, R., Han, Y., & Tang, X. C. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01088-0 · Cited by 85 · see citing works
Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats
Wang, L., Han, Y., & Tang, X. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00291-0 · Cited by 81 · see citing works
Tang, L., Wang, R. T., & Tang, X.-C. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.06.026 · Cited by 79 · see citing works
Fayuk, D. A., & Yakel, J. L. (2004) · Molecular Pharmacology · doi:10.1124/mol.104.000042 · Cited by 72 · see citing works
Zhang, H., Yan, H., & Tang, X. C. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.01.055 · Cited by 70 · see citing works
Gao, X., & Tang, X. C. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20791 · Cited by 68 · see citing works
Myelin proteolipid proteins promote the interaction of oligodendrocytes and axons
Yool, D. A., Klugmann, M., McLaughlin, M., Vouyiouklis, D. A., Dimou, L., Barrie, J. A., McCulloch, M. C., Nave, K., & Griffiths, I. R. (2001) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20010115)63:2 · Cited by 63 · see citing works
Huperzine A attenuates apoptosis and mitochondria‐dependent caspase‐3 in rat cortical neurons
Zhou, J., & Tang, X. C. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03107-1 · Cited by 61 · see citing works
Tang, L., Rui, W. A. N. G., & Tang, X.-C. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00130.x · Cited by 60 · see citing works
Tang, X.-C., Kindel, G. H., Kozikowski, A. P., & Hanin, I. (1994) · Journal of Ethnopharmacology · doi:10.1016/0378-8741(94)01182-6 · Cited by 60 · see citing works
Wang, R. C., Xiao, X., & Tang, X. C. (2001) · Neuroreport · doi:10.1097/00001756-200108280-00009 · Cited by 58 · see citing works
Zhang, H., Liang, Y. Q., Tang, X. C., He, X., & Bai, D. L. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(01)02437-5 · Cited by 56 · see citing works
Pshenichkin, S. P., Szekely, A. M., & Wise, B. C. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63020419.x · Cited by 56 · see citing works
Liang, Y., & Tang, X.-C. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00411.x · Cited by 55 · see citing works
Peng, Y., Jiang, L., Lee, D. Y. W., Schachter, S. C., Ma, Z., & Lemere, C. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20987 · Cited by 53 · see citing works
Saillé, C., Marin, P., Martinou, J., Nicole, A., London, J., & Ceballos-Picot, I. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00089-5 · Cited by 43 · see citing works
The Effect of Cholinesterase Inhibitors on the Secretion of APPS from Rat Brain Cortexa
GIACOBINI, E., MORI, F., & Lai, C. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34451.x · Cited by 42 · see citing works
Second generation cholinesterase inhibitors: Effect of (L)‐huperzine‐A on cortical biogenic amines
Zhu, X. ‐., & Giacobini, E. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490410613 · Cited by 39 · see citing works
Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys
Ou, L. Y., Tang, X. C., & Cai, J. X. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01500-x · Cited by 38 · see citing works
Shang, Y., Ye, J. W., & Tang, X. C. (1999) · PubMed · Cited by 36 · see citing works
Efficacy and tolerability of memantine in the treatment of dementia
Rossom, R. C., Adityanjee, & Dysken, M. W. (2004) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2004.12.006 · Cited by 34 · see citing works
Huperzine A protects rat pheochromocytoma cells against oxygen–glucose deprivation
Zhou, J., Fu, Y., & Tang, X. (2001) · Neuroreport · doi:10.1097/00001756-200107200-00007 · Cited by 27 · see citing works
Li, Y., & Hu, G. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00167-2 · Cited by 22 · see citing works
Huperzine A attenuates the neurotoxic effect of staurosporine in primary rat cortical neurons
Zhang, H., & Tang, X. C. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00023-5 · Cited by 21 · see citing works
Zhang, Y., Chen, X.-Q., Yang, H., Jin, G., Bai, D., & Hu, G. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01615-3 · Cited by 16 · see citing works
Huperzine A inhibits the sustained potassium current in rat dissociated hippocampal neurons
Li, Y., & Hu, G. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00620-1 · Cited by 15 · see citing works
Apoptosis induced by beta-amyloid25-35 in acetylcholinesterase-overexpressing neuroblastoma cells.
Zhang, H. Y., Brimijoin, S., & Tang, X. (2003) · PubMed · Cited by 14 · see citing works
Neurotrophic Factor Strategies for the Treatment of Alzheimer Disease
Nabeshima, T., & Yamada, K. (2000) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200000001-00007 · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 73 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kalaria, R. N., Maestre, G. E., Arizaga, R., Friedland, R. P., Galasko, D., Hall, K., Luchsinger, J. A., Ogunniyi, A., Perry, E. K., Potocnik, F., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70169-8 · Cited by 1,233 · see citing works
Huperzine A from Huperzia species—An ethnopharmacolgical review
Ma, R., Tan, C., Zhu, D., Gang, D. R., & Xiao, P. (2007) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2007.05.030 · Cited by 292 · see citing works
Seltzer, B. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.7.1011 · Cited by 256 · see citing works
A molecular approach in drug development for Alzheimer’s disease
Agatonović-Kuštrin, S., Kettle, C., & Morton, D. W. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.06.147 · Cited by 236 · see citing works
Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer’s Disease
Shal, B., Ding, W., Ali, H., Kim, Y. S., & Khan, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00548 · Cited by 234 · see citing works
Konrath, E. L., Passos, C. D. S., Klein‐Júnior, L. C., & Henriques, A. T. (2013) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12090 · Cited by 219 · see citing works
Venkatesan, R., Ji, E., & Kim, S. Y. (2015) · BioMed Research International · doi:10.1155/2015/814068 · Cited by 212 · see citing works
Where is the hope for drug discovery? Let history tell the future
De, K., Li, X., & Zhang, H. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.07.002 · Cited by 157 · see citing works
Wang, B.-S., Wang, H., Wei, Z.-H., Song, Y., Zhang, L., & Chen, H. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0189-x · Cited by 148 · see citing works
Natural product for the treatment of Alzheimer’s disease
Bui, T. T., & Nguyễn, T. H. (2017) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2016-0147 · Cited by 146 · see citing works
Ansari, N., & Khodagholi, F. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311040005 · Cited by 131 · see citing works
Traditional Chinese medicines and Alzheimer’s disease
Wu, T., Chen, C.-P., & Jinn, T. (2011) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2011.04.004 · Cited by 115 · see citing works
Potential therapeutic targets of huperzine A for Alzheimer's disease and vascular dementia
Zhang, H., Zheng, C. Y., Yan, H., Wang, Z. F., Tang, L. L., Gao, X., & Tang, X. C. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.04.049 · Cited by 111 · see citing works
Arya, A., Chahal, R., Rao, R., Rahman, M. H., Kaushik, D., Akhtar, M. F., Saleem, A., Khalifa, S. M. A., El-Seedi, H. R., Kamel, M., et al. (2021) · Biomolecules · doi:10.3390/biom11030350 · Cited by 111 · see citing works
Wang, C., Zheng, W. H., Wang, T., Xie, J., Wang, S., Zhao, B., Teng, W., & Wang, Z. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.245 · Cited by 107 · see citing works
Huperzine A protects isolated rat brain mitochondria against β-amyloid peptide
Gao, X., Zheng, C. Y., Yang, L., Tang, X. C., & Zhang, H. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.028 · Cited by 103 · see citing works
Wang, Z., Wang, J., Zhang, H., & Tang, X.-C. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05504.x · Cited by 95 · see citing works
Huang, X., Qian, Z., He, X. M., Gong, Q., Wu, K.-C., Jiang, L., Lü, L., Zhu, Z.-J., Zhang, H., Yung, W., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.004 · Cited by 90 · see citing works
Ji, H., & Zhang, H. (2008) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2008.00752.x · Cited by 88 · see citing works
New insights into huperzine A for the treatment of Alzheimer's disease
Zhang, H. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.128 · Cited by 88 · see citing works
Giulia, N., Sestito, S., Digiacomo, M., & Rapposelli, S. (2017) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026617666170607114232 · Cited by 86 · see citing works
Liu, H., Zhao, S., Zhang, Y., Wu, J., Hu, P., Fan, J., & Liao, J. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23303 · Cited by 83 · see citing works
Wang, Z., Qiu, J., Guo, T. B., Liu, A., Wang, Y., Yin, L., & Zhang, J. Z. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.9.5958 · Cited by 81 · see citing works
Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders
Lee, H.-M., & Kim, Y. (2016) · Schizophrenia Research and Treatment · doi:10.1155/2016/6378137 · Cited by 80 · see citing works
Recent Progress in Repositioning Alzheimer'S Disease Drugs Based on a Multitarget Strategy
Santos, M. A., Chand, K., & Chaves, S. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0103 · Cited by 77 · see citing works
Khan, S. A., Ahmad, K., Al-Shammari, E., Adnan, M., Baig, M. H., Lohani, M., Somvanshi, P., & Haque, S. (2015) · BioMed Research International · doi:10.1155/2015/379817 · Cited by 79 · see citing works
Non-cholinergic Effects of Huperzine A: Beyond Inhibition of Acetylcholinesterase
Zhang, H., Yan, H., & Tang, X. C. (2007) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-007-9163-z · Cited by 74 · see citing works
Vascularized neural constructs for ex-vivo reconstitution of blood-brain barrier function
Yue, H., Xie, K., Ji, X., Xu, B., Wang, C., & Shi, P. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.119980 · Cited by 73 · see citing works
Comparative in vitro and in vivo evaluation of lipid based nanocarriers of Huperzine A
Patel, P. A., Patil, S. C., Kalaria, D. R., Kalia, Y. N., & Patravale, V. B. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.02.014 · Cited by 73 · see citing works
Schröder, S., Beckmann, K. H., Franconi, G., Meyer‐Hamme, G., Friedemann, T., Greten, H. J., Rostock, M., & Efferth, T. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/423713 · Cited by 72 · see citing works
Ren, Y., Lü, L., Guo, T. B., Qiu, J., Yang, Y., Liu, A., & Zhang, J. Z. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.1491 · Cited by 70 · see citing works
Catalpol attenuates the neurotoxicity induced by β-amyloid1–42 in cortical neuron–glia cultures
Jiang, B., Du, J., Liu, J., Bao, Y., & An, L. (2007) · Brain Research · doi:10.1016/j.brainres.2007.07.105 · Cited by 65 · see citing works
Kumar, H., More, S. V., Han, S.-D., Choi, J.-Y., & Choi, D. (2012) · Molecules · doi:10.3390/molecules170910503 · Cited by 64 · see citing works
Natural Phenolic Compounds with Neuroprotective Effects
Tavan, M., Hanachi, P., Cádiz‐Gurrea, M. D. L. L., Segura‐Carretero, A., & Mirjalili, M. H. (2023) · Neurochemical Research · doi:10.1007/s11064-023-04046-z · Cited by 62 · see citing works
History and Experience: A Survey of Traditional Chinese Medicine Treatment for Alzheimer′s Disease
Liu, P., Kong, M., Yuan, S., Liu, J., & Wang, P. (2014) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2014/642128 · Cited by 59 · see citing works
Retrospect and prospect of active principles from Chinese herbs in the treatment of dementia
Wang, Y., Huang, L., Tang, X.-C., & Zhang, H. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.46 · Cited by 57 · see citing works
A Systematic Review of Single Chinese Herbs for Alzheimer′s Disease Treatment
Fu, L., & Li, J.-T. (2009) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nep136 · Cited by 57 · see citing works
Bianchi, M. T., Pathmanathan, J. S., & Cash, S. S. (2008) · Medical Hypotheses · doi:10.1016/j.mehy.2008.09.049 · Cited by 56 · see citing works
Vallés, A. S., Borroni, M. V., & Barrantes, F. J. (2014) · CNS Drugs · doi:10.1007/s40263-014-0201-3 · Cited by 55 · see citing works
Yang, L., Ye, C.-Y., Huang, X., Tang, X.-C., & Zhang, H. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120274 · Cited by 55 · see citing works
A robust and scalable synthesis of the potent neuroprotective agent (−)-huperzine A
Tun, M. K. M., Wüstmann, D.-J., & Herzon, S. B. (2011) · Chemical Science · doi:10.1039/c1sc00455g · Cited by 54 · see citing works
Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders
Singh, A. A., Katiyar, S., & Song, M. (2025) · Brain Sciences · doi:10.3390/brainsci15030252 · Cited by 53 · see citing works
Ruan, Q., Hu, X., Ao, H., Ma, H., Gao, Z., Liu, F., Kong, D., Bao, Z., & Yu, Z. (2014) · Gerontology · doi:10.1159/000358235 · Cited by 52 · see citing works
Chang, Y., Shih, Y.-T., Chen, Y.-S., Liu, C., Fang, W.-K., Tsai, C., Tsai, F., Kuo, W., Lai, T.-Y., & Huang, C. (2009) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nep131 · Cited by 52 · see citing works
Gul, A., Bakht, J., & Mehmood, F. (2019) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2018.07.004 · Cited by 52 · see citing works
Tacrine-Based Hybrids: Past, Present, and Future
Bubley, A., Erofeev, A. S., Gorelkin, P. V., Beloglazkina, E. K., Majouga, A. G., & Krasnovskaya, O. O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021717 · Cited by 50 · see citing works
Huperzine A protects C6 rat glioma cells against oxygen–glucose deprivation‐induced injury
Wang, Z. F., & Tang, X. C. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.016 · Cited by 49 · see citing works
Bioprinting Scaffolds for Vascular Tissues and Tissue Vascularization
Hauser, P. V., Chang, H.-M., Nishikawa, M., Kimura, H., Yanagawa, N., & Hamon, M. (2021) · Bioengineering · doi:10.3390/bioengineering8110178 · Cited by 50 · see citing works
Traditional Chinese herbal medicine for vascular dementia
Chan, E. S., Bautista, D. T., Zhu, Y., You, Y., Long, J. T., Li, W., & Chen, C. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010284.pub2 · Cited by 48 · see citing works
Tao, Y., Fang, L., Yang, Y., Jiang, H., Yang, H., Zhang, H., & Zhou, H. (2013) · PROTEOMICS · doi:10.1002/pmic.201200437 · Cited by 47 · see citing works
Zhao, X. D., Liu, C., Yu, Q., Fang, L., Luo, J., Bi, K., & Jia, Y. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9877-z · Cited by 47 · see citing works
Huperzine A for vascular dementia
Hao, Z., Liu, M., Liu, Z., & Lu, D. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007365.pub2 · Cited by 48 · see citing works
Moghaddam, P. M., Sadr, S. S., Roghani, M., Arabzadeh, S., Khamse, S., Zamani, E., Hosseini, M., & Moradi, F. (2019) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13064 · Cited by 46 · see citing works
Gastrodia elata modulates amyloid precursor protein cleavage and cognitive functions in mice
Mishra, M., Huang, J., Lee, Y. Y., Chua, D. S. K., Lin, X., Hu, J., & Heese, K. (2011) · BioScience Trends · doi:10.5582/bst.2011.v5.3.129 · Cited by 44 · see citing works
Progress in the development of new drugs in Alzheimer's disease
Piau, A., Nourhashémi, F., Hein, C., Caillaud, C., & Vellas, B. J. (2011) · The journal of nutrition health & aging · doi:10.1007/s12603-011-0012-x · Cited by 41 · see citing works
Plant derived alkaloids in major neurodegenerative diseases: from animal models to clinical trials
Girdhar, S., Girdhar, A., Verma, S. K., Lather, V., & Pandita, D. (2015) · Journal of Ayurvedic and Herbal Medicine · doi:10.31254/jahm.2015.1307 · Cited by 41 · see citing works
Sun, Y., Wu, X., Ye, Y., Gong, F., Shen, Y., Cai, T., Zhou, X., Wu, X., & Xu, Q. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.08.014 · Cited by 40 · see citing works
Soares, T., Loureiro, L., Carvalho, A. M., Oliveira, M. E. C. D. R., Dias, A. C. P., Sarmento, B. F. C. C., & Lúcio, M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.04.004 · Cited by 37 · see citing works
Shi, J., Liu, Q., Wang, Y., & Luo, G. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.07.004 · Cited by 37 · see citing works
Ghassab‐Abdollahi, N., Mobasseri, K., Ahmadabad, A. D., Nadrian, H., & Mirghafourvand, M. (2021) · Phytotherapy Research · doi:10.1002/ptr.7126 · Cited by 35 · see citing works
Huperzine A for mild cognitive impairment
Yue, J., Dong, B. R., Lin, X., Yang, M. J., Wu, H. M., & Wu, T. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008827.pub2 · Cited by 35 · see citing works
Binding of huperzine A and galanthamine to acetylcholinesterase, based on ONIOM method
Kitisripanya, N., Saparpakorn, P., Wolschann, P., & Hannongbua, S. (2010) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2010.08.004 · Cited by 34 · see citing works
Ji, X., Chi, T., Xu, Q., He, X., Xiao-yu, Z., Zhang, R., & Zou, L. (2014) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2014/969342 · Cited by 34 · see citing works
Callizot, N., Campanari, M., Rouvière, L., Jacquemot, G., Henriques, A. T., Garayev, E., & Poindron, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.681532 · Cited by 34 · see citing works
Herbal medicines to treat Alzheimer's disease
Izzo, A. A., & Capasso, F. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.12.001 · Cited by 34 · see citing works
Ju, D., Kuo, W., Ho, T., Paul, C. R., Kuo, C., Viswanadha, V. P., Lin, C., Chen, Y.-S., Chang, Y., & Huang, C. (2015) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x15500408 · Cited by 33 · see citing works
Progress in acetylcholinesterase inhibitors for Alzheimer's disease: an update
Tumiatti, V., Bolognesi, M. L., Minarini, A., Rosini, M., Milelli, A., Matera, R., & Melchiorre, C. (2008) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.18.4.387 · Cited by 33 · see citing works
Cognitive Enhancers (Nootropics). Part 2: Drugs Interacting with Enzymes
Froestl, W., Muhs, A., & Pfeifer, A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121537 · Cited by 31 · see citing works
Mak, S., Li, W., Fu, H., Luo, J., Cui, W., Hu, S., Pang, Y., Carlier, P. R., Tsim, K. W. K., Pi, R., et al. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15379 · Cited by 30 · see citing works
Chang, Y., Kuo, W., Lai, T.-Y., Shih, Y.-T., Tsai, F., Tsai, C., Shu, W.-T., Chen, Y., Chen, Y.-S., Kuo, W., et al. (2009) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nep216 · Cited by 30 · see citing works
Lei, Y., Yang, L., Ye, C. Y., Qin, M. Y., Yang, H. Y., Jiang, H. L., Tang, X. C., & Zhang, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128366 · Cited by 30 · see citing works
Figueiró, M., Ilha, J., Linck, V. M., Herrmann, A. P., Nardin, P., Menezes, C. B., Achaval, M., Gonçalves, C. A., Porciúncula, L. O., Nunes, D. S., et al. (2010) · Phytomedicine · doi:10.1016/j.phymed.2010.07.013 · Cited by 29 · see citing works
Wang, B., Ye, C., Zhong, X., Chai, Y., Chen, S., & Yuan, R. (2015) · Electroanalysis · doi:10.1002/elan.201500339 · Cited by 28 · see citing works
[+]-Huperzine A Protects Against Soman Toxicity in Guinea Pigs
Wang, Y., Wei, Y., Oguntayo, S., Jensen, N., Doctor, B. P., & Nambiar, M. P. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0564-5 · Cited by 28 · see citing works
Ding, X., Li, X., Liu, D., Cui, W., Ju, X., Wang, S., & Yao, Z. (2012) · Tetrahedron · doi:10.1016/j.tet.2012.05.061 · Cited by 28 · see citing works
Phytomolecules as Alzheimer's therapeutics: A comprehensive review
Hussain, M. K., Ahmad, M., Khatoon, S., Khan, M. V., Azmi, S., Arshad, M., Ahamad, S., & Saquib, M. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117401 · Cited by 27 · see citing works
Cui, W., Cui, G., Li, W., Zhang, Z., Hu, S., Mak, S., Zhang, H., Carlier, P. R., Choi, C., Wong, Y.-T., et al. (2011) · Brain Research · doi:10.1016/j.brainres.2011.05.042 · Cited by 27 · see citing works
Fu, H., Dou, J., Li, W., Cui, W., Mak, S., Hu, Q., Luo, J., Lam, C. S. C., Pang, Y., Youdim, M. B. H., et al. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.09.013 · Cited by 26 · see citing works
Garza, R. D. L., Verrico, C. D., Newton, T. F., Mahoney, J. J., & Thompson-Lake, D. G. Y. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv098 · Cited by 25 · see citing works
Potshangbam, A. M., Polavarapu, R., Rathore, R. S., Naresh, D., Prabhu, N. P., Nongdam, P., Kumar, P., & Vindal, V. (2018) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13430 · Cited by 25 · see citing works
Czapski, G. A., Szypuła, W. J., Kudlik, M., Wileńska, B., Kania, M., Danikiewicz, W., & Adamczyk, A. (2014) · Folia Neuropathologica · doi:10.5114/fn.2014.47840 · Cited by 24 · see citing works
Zhang, J., Zhang, L., Sun, X., Yang, Y., Kong, L., Lu, C., Lv, G., Wang, T., Wang, H., & Fu, F. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.233841 · Cited by 24 · see citing works
Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights
Islam, M. R., Akash, S., Islam, M. M., Sarkar, N., Kumer, A., Chakraborty, S., Dhama, K., Al‐Shaeri, M., Anwar, Y., Wilairatana, P., et al. (2024) · Brain Research · doi:10.1016/j.brainres.2024.148886 · Cited by 27 · see citing works
Bartolini, M., & Marco, J. L. (2018) · The Chemical Record · doi:10.1002/tcr.201800155 · Cited by 23 · see citing works
Rashid, U., & Ansari, F. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50002-7 · Cited by 23 · see citing works
Venkatesan, R., Shim, W., Yeo, E., & Kim, S. Y. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.12.035 · Cited by 21 · see citing works
Mou, X., Pilozzi, A. R., Tailor, B. A., Yi, J., Cahill, C., Rogers, J., & Huang, X.-D. (2020) · Biomedicines · doi:10.3390/biomedicines8030045 · Cited by 18 · see citing works
Zhu, N., Lin, J., Wang, K., Meidan, W., Chen, Q., & Wang, Y. (2015) · Europe PMC (PubMed Central) · Cited by 20 · see citing works
Lu, H., Lü, L., Jiang, M., Dong, Q., & Zheng, G. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s92158 · Cited by 19 · see citing works
Effects of Catalpol on Alzheimer’s Disease and Its Mechanisms
Chen, H., Deng, C., Meng, Z., & Meng, S. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/2794243 · Cited by 19 · see citing works
Role of Phytochemicals in Neurotrophins Mediated Regulation of Alzheimer’s Disease
Sharma, B. (2017) · International Journal of Complementary & Alternative Medicine · doi:10.15406/ijcam.2017.07.00231 · Cited by 19 · see citing works
Phytochemicals as therapeutic interventions in neurodegenerative diseases
Kavitha, R. V., Kumar, J. R., Egbuna, C., & Ifemeje, J. C. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817890-4.00010-x · Cited by 19 · see citing works
Yan, H., Zhang, H. Y., & Tang, X. C. (2007) · Neuroreport · doi:10.1097/wnr.0b013e3280c1e28c · Cited by 19 · see citing works
Huperzine-A, a versatile herb, for the treatment of Alzheimer’s disease
Tsai, S. (2019) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000000151 · Cited by 19 · see citing works
Szypuła, W. J., Wileńska, B., Misicka, A., & Pietrosiuk, A. (2020) · Molecules · doi:10.3390/molecules25143262 · Cited by 18 · see citing works
Lycopodium Alkaloids: Pharmacology
Ólafsdóttir, E. S., Halldorsdottir, E. S., Pich, N., & Ómarsdóttir, S. (2013) · Springer eBooks · doi:10.1007/978-3-642-22144-6_42 · Cited by 18 · see citing works
Ishiuchi, K., Hirose, D., Suzuki, T., Nakayama, W., Jiang, W., Monthakantirat, O., Wu, J., Kitanaka, S., & Makino, T. (2018) · Journal of Natural Products · doi:10.1021/acs.jnatprod.7b00627 · Cited by 17 · see citing works
Huperzine A, but not tacrine, stimulates S100B secretion in astrocyte cultures
Lunardi, P. S., Nardin, P., Guerra, M. C., Abib, R. T., Leite, M. C., & Gonçalves, C. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.01.029 · Cited by 16 · see citing works
Moon, M., Choi, J. G., Kim, S. Y., & Oh, M. S. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140270 · Cited by 16 · see citing works
Terrestrial Plants as a Source of Novel Pharmaceutical Agents
Cragg, G. M. L., Newman, D. J., & Kingston, D. G. I. (2010) · Elsevier eBooks · doi:10.1016/b978-008045382-8.00033-2 · Cited by 16 · see citing works
- Authors
- Zhang, H. Y., & Tang, X. C.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Tang, Xi Can
- ORCID
- Tang, Xi Can
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 27
- Issue
- 12
- Pages
- 619-625
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W1989251920
- Cited by
- 174
- References
- 73
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 10 · 2014: 10 · 2013: 11 · 2012: 12
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- huperzine A, neuroprotection, Alzheimer's disease, acetylcholinesterase inhibition, multi-target therapy, oxidative stress, neuronal apoptosis, nerve growth factor, NGF signaling, learning and memory impairment, neurodegenerative diseases
- MeSH terms
- Alkaloids, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Humans, Sesquiterpenes, Amyloid beta-Protein Precursor, Apoptosis, Neuroprotective Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review