Huperzine A (HupA), extracted from a club moss (Huperzia serrata), is a sesquiterpene alkaloid and a powerful
and reversible inhibitor of acetylcholinesterase (AChE) with on- and off-rates. [6,8] Huperzia has been used in
China for centuries for the treatment of swelling, fever and blood disorders. It has demonstrated both memory
enhancement in animal and clinical trials and neuroprotective effects. [5]
Pharmacokinetics
Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier,
higher oral bioavailability, and longer duration of acetylcholinesterase inhibitory action. [1]
Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that Huperzine A 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. [1]
Pharmacology
Huperzine A has been found to have benefits of reversing or attenuating cognitive deficits in a broad range of
animal models. Clinical trials have demonstrated that Huperzine A relieves memory deficits in aged subjects,
patients with benign senescent forgetfulness, Alzheimer's disease and vascular dementia, with minimal peripheral
cholinergic side effects compared with other AChEIs in use. [2]
Huperzine A possesses the benefits or ability to protect cells against hydrogen peroxide, beta-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, and interfere with APP metabolism. Antagonizing effects on NMDA
receptors and potassium currents may contribute to the neuroprotection as well. It is also possible that the
non-catalytic function of AChE is involved in neuroprotective effects of Huperzine A. The therapeutic effects of
Huperzine A on Alzheimer's disease or vascular dementia are probably exerted via a multi-target mechanism. [2]
Studies about its beneficial claims:
In-vitro Studies
Researchers found that huperzine A protects neurons against Abeta25-35-induced apoptosis via the inhibition of
ROS formation and caspase-3 activity. In the experiment, huperzine A reduced Abeta25-35-induced ROS
formation in a dose-dependent manner. [10]
Treatment of PC12 cells with 10 micromol/L Huperzine A for 48 h markedly increased the number of
neurite-bearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition
to inhibiting AChE activity, 10 micromol/L Huperzine A also increased the mRNA and protein levels of this
enzyme. In addition, following 2 h exposure of the astrocytes to 10 micromol/L Huperzine A, there was a
significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also
increased after 24 h treatment with Huperzine A. Thus, these findings demonstrate that Huperzine has an
neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer
disease. [3]
Animal Studies
L-Huperzine-A was administered systemically or locally through the microdialysis probe into the rat cortex. In both
cases, acetylcholine, norepinephrine and dopamine levels were increased significantly. Thus, L-Huperzine-A is a
potent inhibitor of cholinesterase which penetrates into the brain and produces a dose-dependent increase of
acetylcholine, morepinephrine, and dopamine in rat cortex. [7]
Huperzine A has been shown in animal studies that it can be used as a protective agent against
organophosphate (OP) intoxication and that it reduces glutamate-induced cell death. [5]
Clinical Studies
Huperzine A has undergone double-blind, placebo-controlled clinical trials in patients with Alzheimer's disease
(AD), with significant improvements both to cognitive function and the quality of life. [5]
The therapeutic effects of Huperzine A were studied by random, match and double-blind method on 56 patients
of multi-infarct dementia or senile dementia and 104 patients of senile and presenile simple memory disorders.
The im dose for multi-infarct dementia was 0.05 mg bid for 4 wk, whereas that for senile and presenile simple
memory disorders was 0.03 mg bid for 2 wk. Saline was used on control group. The result showed that the
curative effect of huperzine A was significant. [4]
Safety and Side Effects of Huperzine A
Animal and clinical safety tests showed that Huperzine A had no unexpected toxicity, particularly the dose-limiting
hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that Huperzine A
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. Huperzine A can also be used as a protective agent against organophosphate intoxication. [1,5]
Medications that prevent acetylcholine breakdown often produce side effects, including nausea, vomiting, excess
saliva and tear production, and sweating. In a study of 56 patients suffered from dementia, a few patients felt
slight dizziness. [4]
Reference
SOURCE [1] Wang R, et al, Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese
herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26. [2] Wang R, Neuroprotective effects of huperzine A.
A natural cholinesterase inhibitor for the treatment of Alzheimer's disease. Neurosignals. 2005;14(1-2):71-82. [3]
Tang LL, Wang R, Tang XC. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical
astrocytes and neurite outgrowth in rat PC12 cells. Acta Pharmacol Sin. 2005 Jun;26(6):673-8. [4] Zhang RW, et
al, Drug evaluation of huperzine A in the treatment of senile memory disordersZhongguo Yao Li Xue Bao. 1991
May;12(3):250-2. [5] 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.
2003 Jun;75(3):675-86. [6] Ashani Y, Peggins JO 3rd, Doctor BP. Mechanism of inhibition of cholinesterases by
huperzine A. Biochem Biophys Res Commun. 1992 Apr 30;184(2):719-26. [7] Zhu XD, Giacobini E. Second
generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines. J Neurosci Res. 1995
Aug 15;41(6):828-35. [8] Tang XC. Huperzine A (shuangyiping): a promising drug for Alzheimer's disease.
Zhongguo Yao Li Xue Bao. 1996 Nov;17(6):481-4. [9] Patocka J. Huperzine A--an interesting anticholinesterase
compound from the Chinese herbal medicine. Acta Medica (Hradec Kralove). 1998;41(4):155-7. [10] Xiao XQ,
Zhang HY, Tang XC. Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat
cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res. 2002
Jan 1;67(1):30-6.
and reversible inhibitor of acetylcholinesterase (AChE) with on- and off-rates. [6,8] Huperzia has been used in
China for centuries for the treatment of swelling, fever and blood disorders. It has demonstrated both memory
enhancement in animal and clinical trials and neuroprotective effects. [5]
Pharmacokinetics
Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier,
higher oral bioavailability, and longer duration of acetylcholinesterase inhibitory action. [1]
Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that Huperzine A 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. [1]
Pharmacology
Huperzine A has been found to have benefits of reversing or attenuating cognitive deficits in a broad range of
animal models. Clinical trials have demonstrated that Huperzine A relieves memory deficits in aged subjects,
patients with benign senescent forgetfulness, Alzheimer's disease and vascular dementia, with minimal peripheral
cholinergic side effects compared with other AChEIs in use. [2]
Huperzine A possesses the benefits or ability to protect cells against hydrogen peroxide, beta-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, and interfere with APP metabolism. Antagonizing effects on NMDA
receptors and potassium currents may contribute to the neuroprotection as well. It is also possible that the
non-catalytic function of AChE is involved in neuroprotective effects of Huperzine A. The therapeutic effects of
Huperzine A on Alzheimer's disease or vascular dementia are probably exerted via a multi-target mechanism. [2]
Studies about its beneficial claims:
In-vitro Studies
Researchers found that huperzine A protects neurons against Abeta25-35-induced apoptosis via the inhibition of
ROS formation and caspase-3 activity. In the experiment, huperzine A reduced Abeta25-35-induced ROS
formation in a dose-dependent manner. [10]
Treatment of PC12 cells with 10 micromol/L Huperzine A for 48 h markedly increased the number of
neurite-bearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition
to inhibiting AChE activity, 10 micromol/L Huperzine A also increased the mRNA and protein levels of this
enzyme. In addition, following 2 h exposure of the astrocytes to 10 micromol/L Huperzine A, there was a
significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also
increased after 24 h treatment with Huperzine A. Thus, these findings demonstrate that Huperzine has an
neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer
disease. [3]
Animal Studies
L-Huperzine-A was administered systemically or locally through the microdialysis probe into the rat cortex. In both
cases, acetylcholine, norepinephrine and dopamine levels were increased significantly. Thus, L-Huperzine-A is a
potent inhibitor of cholinesterase which penetrates into the brain and produces a dose-dependent increase of
acetylcholine, morepinephrine, and dopamine in rat cortex. [7]
Huperzine A has been shown in animal studies that it can be used as a protective agent against
organophosphate (OP) intoxication and that it reduces glutamate-induced cell death. [5]
Clinical Studies
Huperzine A has undergone double-blind, placebo-controlled clinical trials in patients with Alzheimer's disease
(AD), with significant improvements both to cognitive function and the quality of life. [5]
The therapeutic effects of Huperzine A were studied by random, match and double-blind method on 56 patients
of multi-infarct dementia or senile dementia and 104 patients of senile and presenile simple memory disorders.
The im dose for multi-infarct dementia was 0.05 mg bid for 4 wk, whereas that for senile and presenile simple
memory disorders was 0.03 mg bid for 2 wk. Saline was used on control group. The result showed that the
curative effect of huperzine A was significant. [4]
Safety and Side Effects of Huperzine A
Animal and clinical safety tests showed that Huperzine A had no unexpected toxicity, particularly the dose-limiting
hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that Huperzine A
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. Huperzine A can also be used as a protective agent against organophosphate intoxication. [1,5]
Medications that prevent acetylcholine breakdown often produce side effects, including nausea, vomiting, excess
saliva and tear production, and sweating. In a study of 56 patients suffered from dementia, a few patients felt
slight dizziness. [4]
Reference
SOURCE [1] Wang R, et al, Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese
herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26. [2] Wang R, Neuroprotective effects of huperzine A.
A natural cholinesterase inhibitor for the treatment of Alzheimer's disease. Neurosignals. 2005;14(1-2):71-82. [3]
Tang LL, Wang R, Tang XC. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical
astrocytes and neurite outgrowth in rat PC12 cells. Acta Pharmacol Sin. 2005 Jun;26(6):673-8. [4] Zhang RW, et
al, Drug evaluation of huperzine A in the treatment of senile memory disordersZhongguo Yao Li Xue Bao. 1991
May;12(3):250-2. [5] 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.
2003 Jun;75(3):675-86. [6] Ashani Y, Peggins JO 3rd, Doctor BP. Mechanism of inhibition of cholinesterases by
huperzine A. Biochem Biophys Res Commun. 1992 Apr 30;184(2):719-26. [7] Zhu XD, Giacobini E. Second
generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines. J Neurosci Res. 1995
Aug 15;41(6):828-35. [8] Tang XC. Huperzine A (shuangyiping): a promising drug for Alzheimer's disease.
Zhongguo Yao Li Xue Bao. 1996 Nov;17(6):481-4. [9] Patocka J. Huperzine A--an interesting anticholinesterase
compound from the Chinese herbal medicine. Acta Medica (Hradec Kralove). 1998;41(4):155-7. [10] Xiao XQ,
Zhang HY, Tang XC. Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat
cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res. 2002
Jan 1;67(1):30-6.
HEALTH BENEFITS OF HUPERZINE A AND ITS SIDE EFFECTS
Huperzia serrata; Herba Huperziae serratae she zu shi shan 蛇足石杉,qian ceng ta,千層塔,Huperszine ARelated
Names: She zu shi shan, 蛇 足 石 杉 ,qian ceng ta 千 層 塔 , jin bu huan, 金不換, qi cun jin 七寸金, qian jin cao 千金草,
she jiao cao 蛇腳草, qian ceng ye, 千層葉, ai song 矮松, shan zhi cao 山芝草, chang bing qian ceng ta, 長柄千層塔
Huperzia serrata; Herba Huperziae serratae she zu shi shan 蛇足石杉,qian ceng ta,千層塔,Huperszine ARelated
Names: She zu shi shan, 蛇 足 石 杉 ,qian ceng ta 千 層 塔 , jin bu huan, 金不換, qi cun jin 七寸金, qian jin cao 千金草,
she jiao cao 蛇腳草, qian ceng ye, 千層葉, ai song 矮松, shan zhi cao 山芝草, chang bing qian ceng ta, 長柄千層塔
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Discuss with your doctor before taking any alternative medicine. This article is for
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