Huperzia serrata

Huperzia serrata

Common Names

  • Chinese club moss
  • Huperzine; Hup A
  • Qian Ceng Ta
  • She Zu Cao
  • Jin Bu Huan; Shan Zhi

For Patients & Caregivers

Huperzine A may help to improve memory. However, it has not been evaluated fully in cancer patients.

Huperzine A is extracted from Huperzia serrata, an herb used in Chinese medicine. It is marketed as a dietary supplement to improve brain function. It may help to improve memory by protecting the nerve cells and has been used as a treatment for Alzheimer’s disease and vascular dementia in Asia. Although some cancer patients use it to reduce brain and nerve side effects from chemotherapy, no clinical studies have been conducted to show it is safe and effective for such use. Huperzine A may interact with many drugs and can cause mild adverse effects.

Although a US patent has been filed claiming Huperzine A for use in cancer pain and neuropathy, it is not an FDA approved drug as no clinical trials for these indications have been conducted.

  • Alzheimer’s disease
    A clinical study showed that Huperzine A may benefit patients with Alzheimer’s disease.
  • Dementia, cognitive decline
    In a clinical study, Huperzine A improved cognition in patients with vascular dementia.
  • Nerve agent poisoning
    Huperzine A was found effective against nerve agent poisoning in animal models.
  • Myasthenia gravis
    Cases of myasthenia gravis have been reported as being treated with huperzine.
  • Neuropathy
    Although claimed to be effective against neuropathy, clinical data is lacking.
  • You are taking an acetylcholinesterase inhibitor drug, like donepezil, galantamine, rivastigmine: Huperzine works by the same mechanism and may increase the risk of adverse effects.
  • You are taking a dopamine D2 receptor blocker: Huperzine A may cause symptoms of Parkinson’s disease.
  • You are using calcium channel blockers or beta adrenergic antagonists: Huperzine A may lower heart rate.

Mild: Nausea, thirst, abdominal pain, anorexia, dizziness, vomiting, constipation, diarrhea, insomnia, excitability, hyperactivity, sweating, slow heart beat, drowsiness, nasal blockage, swelling

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For Healthcare Professionals

Huperzia serrata, Lycopodium serratum

Huperzia serrata, a type of fir moss, is also known as Chinese club moss. It is used as a component in traditional Chinese herbal formulas for blood circulation and to relieve pain. A purified alkaloid extract from this plant known as Huperzine A has neuroprotective effects and has been developed as a treatment for Alzheimer’s disease and dementia in Asia (1). In the US, it is available as a dietary supplement to promote cognitive function. It is also used by some cancer patients to relieve pain and neurological dysfunction due to chemotherapy.

Most studies on H.serrata are based on the extract Huperzine A, which selectively inhibits acetylcholinesterase (1). Animal studies show it has antiapoptotic, anti-inflammatory, and antioxidative properties which contribute to its protective effects in nerve agent poisoning (2), myasthenia gravis (3), hepatic reperfusion injury (4), and diabetes-associated cognitive decline (5). Clinical studies on Huperzine A as a treatment for Alzheimer’s disease have yielded mixed results (6) (7) (8). One study found it to improve cognitive function in vascular dementia patients (9).

Although a US patent has been filed claiming its use for cancer pain and neuropathy (10) , no clinical trials for these indications have been conducted.

Mild adverse effects from Huperzine A have been reported (7). Because it acts as an acetylcholinesterase inhibitor, it can potentially interact with many drugs including other anticholinergic drugs, dopamine D2 receptor blockers, calcium channel blockers, and beta adrenergic receptor antagonists (11).

  • Alzheimer’s disease
  • Dementia, cognitive decline
  • Nerve agent poisoning
  • Myasthenia gravis
  • Neuropathy

Huperzine A is an acetylcholinesterase inhibitor, raising the levels of acetylcholine in the basal ganglia  (1). Higher levels of acetylcholine in the central nervous system are believed to be responsible for less severe cognitive impairment in Alzheimer’s disease (1). Additionally, Huperzine A can interfere with the pathway of beta-amyloid deposition by regulating precursor protein metabolism and impeding associated neurotoxicity (13). Huperzine A also inhibits the N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex (14).

Huperzine A diminished diabetes-associated cognitive decline in rats by enhancing glycemic control, suppressing inflammation, augmenting brain-derived neurotrophic factor expression, and limiting oxidative stress (5). In a mouse model of hepatic ischemia reperfusion injury, the antioxidative, anti-inflammatory, and antiapoptotic properties of Huperzine A contributed to hepatoprotective effects (4).

Nausea, anorexia, dizziness, vomiting, constipation, insomnia, excitability, thirst, sweating, bradycardia, abdominal pain, somnolence, hyperactivity, nasal obstruction, diarrhea, and edema (21). Some of these reactions could stem from the anticholinesterase activity of Huperzine A.

Cytochrome P450 substrates: Huperzine A induces CYP3A4 by activating pregnane X receptor (22). This may reduce the effectiveness of drugs metabolized by this enzyme.
Acetylcholinesterase inhibitors (Donepezil, galantamine, rivastigmine): Huperzine A may increase the risk of adverse events for other drugs that have acetylcholinesterase inhibition effects.
Dopamine D2 receptor blockers: Taken in conjunction with acetylcholinesterase inhibitors can produce a dopamine/acetylcholine imbalance in the striatum, leading to parkinsonian symptoms (11).
Calcium channel blockers: Because acetylcholinesterase inhibitors can produce bradycardia on their own, Huperzine A and a calcium channel blocker may produce a more severe bradycardia (11).
Beta adrenergic receptor antagonists: Because acetylcholinesterase inhibitors can produce bradycardia on their own, Huperzine A and a calcium channel blocker may produce a more severe bradycardia (11).

  1. Xing SH, Zhu CX, Zhang R, et al. Huperzine a in the treatment of Alzheimer’s disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med. 2014;2014:363985. doi: 10.1155/2014/363985

  2. Wang Y, Wei Y, Oguntayo S, et al. A combination of [+] and [-]-Huperzine A improves protection against soman toxicity compared to [+]-Huperzine A in guinea pigs. Chem Biol Interact. Mar 25 2013;203(1):120-124. doi: 10.1016/j.cbi.2012.10.016

  3. Ma X, Tan C, Zhu D, et al. Huperzine A from Huperzia species—an ethnopharmacolgical review. J Ethnopharmacol. Aug 15 2007;113(1):15-34. doi: 10.1016/j.jep.2007.05.030

  4. Yang Y, Yang J, Jiang Q. The protective effect of huperzine A against hepatic ischemia reperfusion injury in mice. Transplant Proc. Jun 2014;46(5):1573-1577. doi: 10.1016/j.transproceed.2014.01.018

  5. Mao XY, Cao DF, Li X, et al. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Int J Mol Sci. 2014;15(5):7667-7683. doi: 10.3390/ijms15057667

  6. Desilets AR, Gickas JJ, Dunican KC. Role of huperzine a in the treatment of Alzheimer’s disease. Ann Pharmacother. Mar 2009;43(3):514-518. doi: 10.1345/aph.1L402

  7. Li J, Wu HM, Zhou RL, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev. 2008(2):CD005592. doi: 10.1002/14651858.CD005592.pub2

  8. Rafii MS, Walsh S, Little JT, et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology. Apr 19 2011;76(16):1389-1394. doi: 10.1212/WNL.0b013e318216eb7b

  9. Xu ZQ, Liang XM, Juan W, et al. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys. Jan 2012;62(1):55-58. doi: 10.1007/s12013-011-9258-5

  10. Schachter (Inventor). Use of huperzine for neuropathic pain. US Patent No 8,193,212. Cambridge, MA: President and Fellows of Harvard College, assignee; 2012.

  11. Bentue-Ferrer D, Tribut O, Polard E, et al. Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs. 2003;17(13):947-963.

  12. Zhang HY, Yan H, Tang XC. Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cell Mol Neurobiol. Feb 2008;28(2):173-183. doi: 10.1007/s10571-007-9163-z

  13. Wang XD, Zhang JM, Yang HH, et al. Modulation of NMDA receptor by huperzine A in rat cerebral cortex. Zhongguo Yao Li Xue Bao. Jan 1999;20(1):31-35.

  14. Li YX, Zhang RQ, Li CR, et al. Pharmacokinetics of huperzine A following oral administration to human volunteers. Eur J Drug Metab Pharmacokinet. Oct-Dec 2007;32(4):183-187.

  15. Wang Q, Chen G. Pharmacokinetic behavior of huperzine A in plasma and cerebrospinal fluid after intranasal administration in rats. Biopharm Drug Dispos. Dec 2009;30(9):551-555. doi: 10.1002/bdd.686

  16. Burshtein G, Friedman M, Greenberg S, et al. Transepithelial transport of a natural cholinesterase inhibitor, huperzine A, along the gastrointestinal tract: the role of ionization on absorption mechanism. Planta Med. Mar 2013;79(3-4):259-265. doi: 10.1055/s-0032-1328128

  17. Ma X, Wang H, Xin J, et al. Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A. Eur J Pharmacol. Feb 14 2003;461(2-3):89-92.

  18. Wang R, Yan H, Tang X. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26. .

  19. Chen JK. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press, Inc; 2004.

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