Phytochemistry Reviews

, Volume 15, Issue 1, pp 51–85 | Cite as

Huperzine A from Huperzia serrata: a review of its sources, chemistry, pharmacology and toxicology

  • Ana Ferreira
  • Márcio Rodrigues
  • Ana Fortuna
  • Amílcar Falcão
  • Gilberto AlvesEmail author


The use and popularity of herbal medicines has been increasing worldwide. In fact, today, the traditional Chinese medicine offers a vast repertory for pharmaceutical research, as is the case of Huperzia serrata, a member of Huperziaceae family. This review reports the Lycopodium alkaloids that have been isolated from this plant. However, it was mainly focused on the huperzine A (HupA), a promising therapeutic option in several acute and chronic disorders. The major therapeutic interest described for HupA has been directed to the treatment of acetylcholine-deficit dementia, including Alzheimer’s disease. However, HupA was also shown to be effective on cerebrovascular dementia and other neurodegenerative disorders with an ischemic component, as well as on other kind of cognitive impairments; the value of HupA on myasthenia gravis, organophosphate poisoning and schizophrenia has also been described. In addition, many other pharmacological properties have been ascribed to HupA, namely its anti-inflammatory, antinociceptive and anticonvulsant properties, which was recently identified, promoting a growing interest on HupA research. Furthermore, its particular chemical structure and the fact that HupA is well tolerated in humans, even at doses well above those clinically required, along with its favorable pharmacokinetics, also boosted an intense research in the pharmaceutical industry. Therefore, several HupA-related features are addressed in this review, including not only its therapeutic properties, but also its chemistry, biological and chemical sources, structure–activity relationship, pharmacokinetics and toxicology, which are discussed in detail covering the literature published from 1962 to 2014.


Huperziaceae Huperzia serrata Lycopodium alkaloids Huperzine A Alzheimer’s disease 







Alzheimer’s disease






Peak concentration


Central nervous system


Cytochrome P450


Huperzine A








Median lethal dose




Per os





The authors thank the support of Fundação para a Ciência e a Tecnologia (FCT, Portugal) through the fellowship SFHR/BD/84936/2012, involving the POPH (Programa Operacional Potencial Humano) which is co-funded by FSE (Fundo Social Europeu), and through the strategic project Pest-OE/SAU/UI0709/2014.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Ana Ferreira
    • 1
    • 2
  • Márcio Rodrigues
    • 1
    • 2
    • 3
  • Ana Fortuna
    • 2
    • 3
  • Amílcar Falcão
    • 2
    • 3
  • Gilberto Alves
    • 1
    • 2
    Email author
  1. 1.CICS-UBI – Health Sciences Research Centre, Faculty of Health SciencesUniversity of Beira InteriorCovilhãPortugal
  2. 2.CNC – Centre for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  3. 3.Laboratory of Pharmacology, Faculty of PharmacyUniversity of CoimbraCoimbraPortugal

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