Cited by 470Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsMedicinal Plants and Neuroprotection

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

WANG, Rui, YAN, Han, TANG, Xi-can·2006·Acta Pharmacologica Sinica

Abstract

Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase(AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

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Crossref · 10.1111/j.1745-7254.2006.00255.x

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Authors
WANG, R., YAN, H., & TANG, X.-C.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
TANG, Xi-can
Venue
Acta Pharmacologica Sinica
Published
2006-01
Volume
27
Issue
1
Pages
1-26
ISSN
  • 0253-9756 (ISSN-L)
  • 1671-4083
  • 1745-7254
OpenAlex
W2004554863
Cited by
470
References
157
Citations by year
2026: 11 · 2025: 19 · 2024: 14 · 2023: 10 · 2022: 28 · 2021: 29 · 2020: 21 · 2019: 28 · 2018: 23 · 2017: 27 · 2016: 34 · 2015: 21 · 2014: 27 · 2013: 32 · 2012: 22
FWCI
2.70
Type
journal article
Language
en
Open access
closed
Locations
  • Acta Pharmacologica Sinica (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, Huperzia serrata, acetylcholinesterase inhibitors, cholinesterase inhibitors, neuroprotection, Alzheimer's disease, vascular dementia, memory impairment, oxidative stress, apoptosis, NMDA receptor, potassium currents, APP processing, organophosphate poisoning, pharmacokinetics
MeSH terms
Alkaloids, Alzheimer Disease, Animals, Brain, Cholinesterase Inhibitors, Cholinesterases, Cognition, Humans, Sesquiterpenes, Dementia, Vascular, Apoptosis, Oxidative Stress, Neuroprotective Agents

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