Skip to main content
SpringerLink
Log in

Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis

Journal of Neural Transmission Aims and scope Submit manuscript

Cite this article

Abstract

The objective of this study was to provide an updated meta-analysis of the efficacy and safety of huperzine A (HupA) in Alzheimer’s disease (AD). We searched for randomized trials comparing HupA with placebo in the treatment of AD. The primary outcome measures were mini-mental state examination (MMSE) and activities of daily living scale (ADL). Data were extracted from four randomized clinical trials and analyzed using standard meta-analysis and meta-regression methods. Oral administration of HupA for 8–24 weeks (300–500 μg daily) led to significant improvements in MMSE and ADL. The results of meta-regression showed that the estimated effect size of MMSE and ADL was increased over the treatment time. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug that could significantly improve cognitive performance and ADL in patients with AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Bai DL, Tang XC, He XC (2000) Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr Med Chem 7:355–374

    PubMed  CAS  Google Scholar 

  • Chen MJ, Gao ZX, Deng HY, Liu FG (2000) A multi-center, double-blind clinical trial of huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Chin J New Drugs Clin Rem 19:10–12

    Google Scholar 

  • Dong HT, Jin YG, Bai Y (2002) 11 cases of Alzheimer’s disease treated by acupuncture. Acta Universitatis Traditionis Medicalis Sinensis Pharmacologiaeque Shanghai 16:26–28

    Google Scholar 

  • Follmann D, Elliott P, Suh I, Cutler J (1992) Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 45:769–773

    Article  PubMed  CAS  Google Scholar 

  • Folstein M, Folstein S, McHugh P (1975) The mini-mental state examination. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  • Giacobini E (2004) Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res 50:433–440

    Article  PubMed  CAS  Google Scholar 

  • Isaac MG, Quinn R, Tabet N (2008) Vitamin E for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev (3). Art. No.: CD002854. doi: 10.1002/14651858.CD002854

  • Kelley BJ, Knopman DS (2008) Alternative medicine and Alzheimer disease. Neurologist 14:299–306

    Article  PubMed  Google Scholar 

  • Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186

    PubMed  CAS  Google Scholar 

  • Li J, Wu HM, Zhou RL, Liu GJ, Dong BR (2008) Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev (2). Art. No.: CD005592. doi:10.1002/14651858.CD005592

  • Little JT, Walsh S, Aisen PS (2008) An update on huperzine A as a treatment for Alzheimer’s disease. Expert Opin Investig Drugs 17:209–215

    Article  PubMed  CAS  Google Scholar 

  • Liu FG, Fang YS, Gao ZX, Zhou JD, Su ML (1995) Double-blind control treatment of huperzine-A and placebo in 28 patients with Alzheimer disease. Chin J Pharmacoepidemiol 4:196–197

    Google Scholar 

  • Ma X, Tan C, Zhu D, Gang DR, Xiao P (2007) Huperzine A from Huperzia species—an ethnopharmacolgical review. J Ethnopharmacol 113:15–34

    Article  PubMed  CAS  Google Scholar 

  • Mazurek A (2000) An open-label trial of huperzine A in the treatment of Alzheimer’s disease. Altern Ther Health Med 5:97–98

    Google Scholar 

  • Normand SLT (1999) Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med 18:321–359

    Article  PubMed  CAS  Google Scholar 

  • Rogers SL, Doody RS, Hohs RC, Friedhoff LT, Donepezil Study Group (1998a) Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind placebo-controlled study. Arch Intern Med 158:1021–1031

    Article  PubMed  CAS  Google Scholar 

  • Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT (1998b) A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 50:136–145

    PubMed  CAS  Google Scholar 

  • Schneider LS (2001) Assessing outcomes in Alzheimer disease. Alzheimer Dis Assoc Disord 15:S8–S18

    Article  PubMed  Google Scholar 

  • Tang XC, De Sarno P, Sugaya K, Giacobini E (1989) Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat. J Neurosci Res 24:276–285

    Article  PubMed  CAS  Google Scholar 

  • Thompson SG, Higgins JP (2002) How should meta-regression analyses be undertaken and interpreted? Stat Med 21:1559–1573

    Article  PubMed  Google Scholar 

  • Van Houwelingen HC, Arends LR, Stijnen T (2002) Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med 21:589–624

    Article  PubMed  Google Scholar 

  • Ved HS, Koenig ML, Dave JR, Doctor BP (1997) Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport 8:963–968

    Article  PubMed  CAS  Google Scholar 

  • Wang R, Yan H, Tang XC (2006) Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 27:1–26

    Article  PubMed  Google Scholar 

  • Whitehead A (2002) Meta-analysis of controlled clinical trial. Wiley, Chichester

    Book  Google Scholar 

  • Wong DM, Greenblatt HM, Dvir H, Carlier PR, Han YF, Pang YP, Silman I, Sussman JL (2003) Acetylcholinesterase complexed with bivalent ligands related to huperzine a: experimental evidence for species-dependent protein-ligand complementarity. J Am Chem Soc 125:363–373

    Article  PubMed  CAS  Google Scholar 

  • Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS, Li SL (1995) Efficacy of tablet huperzine A on memory, cognition, and behavior in Alzheimer’s disease. Acta Pharmacol Sin 16:391–395

    CAS  Google Scholar 

  • Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B (1999) Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Acta Pharmacol Sin 20:486–490

    CAS  Google Scholar 

  • Yan H, Tang XC (2006) Review on clinical application of huperzine A in China. Chin J New Drugs Clin Rem 25:682–687

    CAS  Google Scholar 

  • Yang JS, Jiang ZH (1996) The clinical report of the effect of huperzine A in treatment of Alzheimer’s disease. Heibei Jing Shen Wei Sheng 9:84–85

    Google Scholar 

  • Yang CY, Lu ZP, Zheng CG (2003) Efficacy and reliability of huperzine A in mild and moderate Alzheimer’s disease. Chin J Clin Rehabil 7:4258–4259

    Google Scholar 

  • Zhang HY, Tang XC (2006) Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends Pharmacol Sci 27:619–625

    Article  PubMed  CAS  Google Scholar 

  • Zhang ZX, Wang XD, Chen QT, Shu L, Wang JZ, Shan GL (2002) Clinical efficacy and safety of huperzine A in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. Zhonghua Yi Xue Za Zhi 82:941–944

    PubMed  CAS  Google Scholar 

  • Zhang ML, Yuan GZ, Yao JJ, Bi P, Ni SQ (2006) Evaluation of clinical effect and safety of huperzine A in treating 52 Alzheimer’s disease. Chin J New Drugs Clin Rem 25:693–695

    CAS  Google Scholar 

  • Zhang HY, Zheng CY, Yan H, Wang ZF, Tang LL, Gao X, Tang XC (2008) Potential therapeutic targets of huperzine A for Alzheimer’s disease and vascular dementia. Chem Biol Interact 175:396–402

    Article  PubMed  CAS  Google Scholar 

  • Zhou BR, Xu ZQ, Kuang YF, Deng YH (2004) Curative effect of aspirin for postponing the development of Alzheimer’s disease. Chin J Clin Rehabil 8:3020–3021

    Google Scholar 

Download references

Acknowledgments

We gratefully thank the National Natural Science Foundation of China (No. 30772553), the Program of Shanghai Subject Chief Scientist (06XD14011), the Major Basic Research Project of Shanghai Municipal Science and Technology Commission (07DJ14005) and Shanghai Rising-Star Program (08QA14042) for financial support.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Biostatistics, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 200025, Shanghai, China

    Bai-song Wang, Hao Wang, Zhao-hui Wei, Yan-yan Song & Hong-zhuan Chen

  2. Department of Biomedical Engineering, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 200025, Shanghai, China

    Lu Zhang

Authors
  1. Bai-song Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhao-hui Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan-yan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-zhuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong-zhuan Chen.

Additional information

B.-s. Wang and H. Wang contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, Bs., Wang, H., Wei, Zh. et al. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis. J Neural Transm 116, 457–465 (2009). https://doi.org/10.1007/s00702-009-0189-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-009-0189-x

Keywords

search

Navigation