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Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine
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  • Review
  • Published: 01 January 2006

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

  • Rui Wang1,
  • Han Yan1 &
  • Xi-can Tang1 

Acta Pharmacologica Sinica volume 27, pages 1–26 (2006)Cite this article

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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, β-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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Authors and Affiliations

  1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201203, China

    Rui Wang, Han Yan & Xi-can Tang

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  1. Rui Wang
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  2. Han Yan
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Correspondence to Xi-can Tang.

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Project supported in part by the grants from Ministry of Science and Technology of China (G1998051110, G1998051115, 2004CB518907) and the National Natural Science Foundation of China (No 39170860, 39770846, 3001161954, 30123005, 30271496, and 30572169).

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Wang, R., Yan, H. & Tang, Xc. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 27, 1–26 (2006). https://doi.org/10.1111/j.1745-7254.2006.00255.x

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  • Received: 05 October 2005

  • Accepted: 20 October 2005

  • Issue Date: 01 January 2006

  • DOI: https://doi.org/10.1111/j.1745-7254.2006.00255.x

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Keywords

  • huperzine A
  • Alzheimer disease
  • acetylcholinesterase
  • cholinesterase inhibitors
  • cognitive enhancer
  • neuroprotect agents
  • oxidative stress
  • apoptosis

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