Huperzia serrata

Purported Benefits, Side Effects & More

Huperzia serrata

Purported Benefits, Side Effects & More
Huperzia serrata

Common Names

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

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Huperzine A may help improve memory, but studies are limited with mixed results.

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 nerve cells and has been used as a treatment for Alzheimer’s disease and vascular dementia in Asia. However, larger well-designed studies are needed.

Although some cancer patients use huperzine to reduce chemotherapy side effects, no clinical studies have been conducted to show it is safe and effective for such use. It may also interact with many drugs and can cause mild adverse effects.

What are the potential uses and benefits?
  • To treat cognitive disorders

    Studies on whether huperzine may benefit patients with Alzheimer's disease are mixed. It may improve cognition in patients with vascular dementia, but additional studies are needed.
  • To treat myasthenia gravis

    Cases of this neuromuscular disease have been reported as being treated with huperzine.
  • To relieve neuropathy

    Although there are claims of effectiveness against neuropathy, clinical data are lacking.
What are the side effects?

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

What else do I need to know?

Do Not Take if:

  • You are taking acetylcholinesterase inhibitor drugs like donepezil, galantamine, or rivastigmine: Huperzine works by the same mechanism and may increase the risk of adverse effects.
  • You are taking a dopamine D2 receptor blocker: Huperzine may cause symptoms of Parkinson’s disease.
  • You are using calcium channel blockers or beta adrenergic antagonists: Huperzine may lower heart rate.

For Healthcare Professionals

Scientific Name
Huperzia serrata, Lycopodium serratum
Clinical Summary

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 suggest antiapoptotic, anti-inflammatory, and antioxidative properties may 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 for Alzheimer’s disease have yielded mixed results (6) (7) (8), but a meta-analysis suggests that it may help mild to moderate cognitive dysfunction (24). One study found it improved cognitive function in vascular dementia patients (9). More well-designed studies are needed to determine safety and effectiveness.

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 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).

Purported Uses and Benefits
  • Cognitive disorders
  • Myasthenia gravis
  • Neuropathy
Mechanism of Action

Huperzine A is an acetylcholinesterase inhibitor, thereby raising acetylcholine levels 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 can interfere with the pathway of beta-amyloid deposition by regulating precursor protein metabolism and impeding associated neurotoxicity (13). Huperzine also inhibits the N-methyl-D-aspartate receptors in the cerebral cortex (14).

Huperzine 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 contributed to hepatoprotective effects (4).

Adverse Reactions

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.

Herb-Drug Interactions

CYP450 substrates: Lab studies indicate huperzine A induces CYP3A4 by activating pregnane X receptor (22). This may reduce effectiveness of drugs metabolized by this enzyme. Clinical relevance has yet to be determined.
Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine): Huperzine A may increase risk of adverse events for other drugs that have acetylcholinesterase inhibition effects.
Dopamine D2 receptor blockers: Taken in conjunction with acetylcholinesterase inhibitors, it may 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 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 more severe bradycardia (11).

Dosage (OneMSK Only)
  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.
  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.
  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.
  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.
  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.
  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.
  7. Li J, Wu HM, Zhou RL, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev. 2008(2):CD005592.
  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.
  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.
  10. Schachter (Inventor). Use of huperzine for neuropathic pain. Harvard College, assignee.
  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. Zangara A. The psychopharmacology of huperzine A: An alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s disease. Pharmacol Biochem Behav. Jun 2003;75(3):675-686.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. Jiang H, Luo X, Bai D. Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer’s disease. Curr Med Chem. Nov 2003;10(21):2231-2252.
  19. 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.
  20. 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. .
  21. Yang G, Wang Y, Tian J, et al. Huperzine a for Alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2013;8(9):e74916.
  22. Zhang YW, Bao MH, Wang G, et al. Induction of human CYP3A4 by huperzine A, ligustrazine and oridonin through pregnane X receptor-mediated pathways. Pharmazie. Jul 2014;69(7):532-536.
  23. Chen JK. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press, Inc; 2004.
  24. Cui CC, Sun Y, Wang XY, et al. The effect of anti-dementia drugs on Alzheimer disease-induced cognitive impairment: A network meta-analysis. Medicine (Baltimore). Jul 2019;98(27):e16091.
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