Pharmacological Profile of Huperzine A, a Novel Acetylcholinesterase Inhibitor from Chinese Herb

Exposure to aluminum has been correlated with the epidemiology of Alzheimer’s disease. Huperzine A (HupA), derived from the Chinese herb Huperzia serrata, is an inhibitor of acetylcholinesterase (AChE). However, its use in aluminum induced neurotoxicity has not been reported. The objective of the study was to examine the effect of HupA on aluminum-induced changes in AChE activity and hippocampal neurotoxicity. Aged female swiss albino mice were divided into five groups (n=10). Aluminum treated group (Al-S) received 30 mg/Kg of aluminum chloride (AlCl3) intraperitoneally (IP) for two weeks followed by IP normal saline. Three HupA treated groups received similar IP dosage of AlCl3 for two weeks followed by HupA 0.1 mg/Kg, HupA 0.2 mg/Kg and HupA 0.5 mg/kg. Control group received IP normal saline. At the end of week 4, AChE was estimated, and pyramidal neurons of hippocampus were counted. Al-S group showed an increase in mean brain AChE and Al-HupA 0.1 reduced it significantly (p<0.05). Reduction in mean neuronal density in Al-S group, was comparatively more in CA3 hippocampal area (p<0.001). Quantitative study found that 0.2mg/Kg of synthetic Huperzine A given intraperitoneally, was able to increase neuronal count significantly compared to 0.1mg/Kg and 0.5mg/Kg of Huperzine A.

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Primary Investigation for the Mechanism of Biatractylolide fromAtractylodis Macrocephalae Rhizomaas an Acetylcholinesterase Inhibitor

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/7481323 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Yong-Chao Xie ◽

Ning Ning ◽

Li Zhu ◽

Dan-Ning Li ◽

Xing Feng ◽

...

Keyword(s):

Molecular Docking ◽

Molecular Mechanisms ◽

Acetylcholinesterase Inhibitor ◽

Huperzine A ◽

Dependent Manner ◽

H Nmr ◽

Sites Of Action ◽

Dose Dependent ◽

Ache Expression ◽

C Nmr

Biatractylolide was isolated from ethyl acetate extract of driedAtractylodis Macrocephalae Rhizomaroot by multistep chromatographic processing. Structure of biatractylolide was confirmed by1H-NMR and13C-NMR. The IC50on acetylcholinesterase (AChE) activity was 6.5458 μg/mL when the control IC50value of huperzine A was 0.0192 μg/mL. Molecular Docking Software (MOE) was used to discover molecular sites of action between biatractylolide and AChE protein by regular molecular docking approaches. Moreover, biatractylolide downregulated the expression of AChE of MEF and 293T cells in a dose-dependent manner. These results demonstrated that the molecular mechanisms of inhibitory activities of biatractylolide on AChE are not only through binding to AChE, but also via reducing AChE expression by inhibiting the activity of GSK3β.

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ChemInform Abstract: Huperzine A - A Potent Acetylcholinesterase Inhibitor of Use in the Treatment of Alzheimer′s Disease.

ChemInform ◽

10.1002/chin.199129273 ◽

2010 ◽

Vol 22 (29) ◽

pp. no-no

Author(s):

S. J. GEIB ◽

W. TUECKMANTEL ◽

A. P. KOZIKOWSKI

Keyword(s):

Acetylcholinesterase Inhibitor ◽

Huperzine A

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Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice

Neural Plasticity ◽

10.1155/2015/453170 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Zhen-Xing Zuo ◽

Yong-Jie Wang ◽

Li Liu ◽

Yiner Wang ◽

Shu-Hao Mei ◽

...

Keyword(s):

Mechanical Allodynia ◽

Acetylcholine Receptors ◽

Chinese Herb ◽

Competitive Inhibitor ◽

Place Preference ◽

Muscarinic Acetylcholine Receptors ◽

Anterior Cingulate ◽

Huperzine A ◽

Spontaneous Pain ◽

Withdrawal Threshold

Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herbHuperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear. We evaluated the effects of Hup A on spontaneous pain in mice using the conditioned place preference (CPP) behavioral assay and found that application of Hup A attenuated the mechanical allodynia induced by peripheral nerve injury or inflammation. This effect was blocked by atropine. However, clonidine but not Hup A induced preference for the drug-paired chamber in CPP. The same effects occurred when Hup A was infused into the anterior cingulate cortex. Furthermore, ambenonium chloride, a competitive inhibitor of acetylcholinesterase, also increased the paw-withdrawal threshold but failed to induce place preference in CPP. Therefore, our data suggest that acetylcholinesterase in both the peripheral and central nervous systems is involved in the regulation of mechanical allodynia but not the spontaneous pain.

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Huperzine A – a potent acetylcholinesterase inhibitor of use in the treatment of Alzheimer's disease

Acta Crystallographica Section C Crystal Structure Communications ◽

10.1107/s0108270190008952 ◽

1991 ◽

Vol 47 (4) ◽

pp. 824-827 ◽

Cited By ~ 13

Author(s):

S. J. Geib ◽

W. Tückmantel ◽

A. P. Kozikowski

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Acetylcholinesterase Inhibitor ◽

Huperzine A

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Qualification and quantification of huperzine a from Huperia serrata in Da Lat, Lam Dong province

Vietnam Journal of Biotechnology ◽

10.15625/1811-4989/14/3/9861 ◽

2016 ◽

Vol 14 (3) ◽

pp. 473-478 ◽

Cited By ~ 1

Author(s):

Vũ Thị Ngọc ◽

Phạm Thị Hạnh ◽

Lê Thị Lan Anh ◽

Nguyễn Tiến Đạt ◽

Lê Thị Bích Thủy

Keyword(s):

High Performance ◽

Elderly Population ◽

Acetylcholinesterase Inhibitor ◽

Acetylcholinesterase Activity ◽

The Elderly ◽

Hplc Method ◽

Huperzine A ◽

Huperzia Serrata ◽

Layer Chromatography ◽

Hplc Data

Huperzine A, an alkaloid, was originally isolated from Huperzia serrata. This compound potentially enhances the memory in animal, hence, it has been approved as a drug for the clinical treatment of Alzheimer’s disease, a major disease affecting the elderly population throughout the world. Because Huperzine A is an acetylcholinesterase inhibitor, the presentation of Huperzine A in brain inhibited acetylcholinesterase activity, thus, leading to the increase in concentration of acetylcoline. In Vietnam, H. serrata distributed in Sapa (Lao Cai) and Da Lat (Lam Dong), this species provide valuable pharmaceutical materials to the treatment for Alzheimer’s diseases. In this research, we evaluated the availability of Huperzine A in Huperzia serrata, which was collected from Da Lat (Lam Dong) in two seasons: Spring and Autunm. Thin layer chromatography (TLC) method was used to preliminary qualitative analysis. High performance liquid chromatography (HPLC) method were used for determining Huperzine A content in samples. In the result, Huperzine A is almost existed in leaves of Da Lat Huperzia serrata and equivalent levels of Chinese Huperzia serrata. The Content of Huperzine A was different between two collection samples in Spring and Autumn, by analyze HPLC data, the samples was harvested in Autumn contents 92.5 µg.g-1dry sample and the spring is 75.4 µg.g-1 dry sample. Therefore, the content of Huperzine A in Huperzia serrata’s leaves sample is harvested in the fall compared with samples collected in the spring is higher 17.1 µg.g-1dry samples.

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