Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1
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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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 [134]
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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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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.
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