Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease

• Published in: Neuro-Signals Vol. 14; no. 1-2; p. 71
• Main Authors: Wang, Rui, Tang, Xi Can
• Format: Journal Article
• Language: English
• Published: Switzerland 2005
• Subjects: Alkaloids; Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Alzheimer Disease - physiopathology; Animals; Brain Chemistry - drug effects; Brain Chemistry - physiology; Cell Death - drug effects; Cell Death - physiology; Cerebrovascular Disorders - drug therapy; Cerebrovascular Disorders - enzymology; Cerebrovascular Disorders - physiopathology; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - therapeutic use; Humans; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 1424-862X
• DOI: 10.1159/000085387

Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase. It has been found to reverse or attenuate cognitive deficits in a broad range of animal models. Clinical trials in China have demonstrated that HupA significantly relieves memory deficits in aged subjects, patients with benign senescent forgetfulness, Alzheimer's disease (AD) and vascular dementia (VD), with minimal peripheral cholinergic side effects compared with other AChEIs in use. HupA possesses the 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 HupA. The therapeutic effects of HupA on AD or VD are probably exerted via a multi-target mechanism.