Huperzine A attenuates amyloid β-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation
✍ Scribed by Xiao Qiu Xiao; Hai Yan Zhang; Xi Can Tang
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 370 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Huperzine A, a novel Lycopodium alkaloid originally discovered in the Chinese herb Qian Ceng Ta (Huperzia serrata), is a reversible, potent, and selective acetylcholinesterase (AChE) inhibitor and has been extensively used for the treatment of Alzheimer's disease (AD) in China. The present studies were designed to investigate effects of huperzine A on amyloid β‐peptide fragment 25‐35 (Aβ25‐35)‐induced neuronal apoptosis and potential mechanisms in primary cultured rat cortical neurons. After exposure of the cells to Aβ25‐35 (20 μM), apoptotic cell death was observed as evidenced by a significant decrease in cell viability, alteration of neuronal morphology, and DNA fragmentation. Pretreatment of the cells with huperzine A (0.01–10 μM) prior to Aβ25‐35 exposure significantly elevated the cell survival and reduced Aβ25‐35‐induced nuclei fragmentation. Reactive oxygen species (ROS)‐based fluorescence, caspase‐3‐like fluorogenic cleavage, and Western blot analysis demonstrated that huperzine A reduced Aβ25‐35‐induced ROS formation in a dose‐dependent manner, and 1 μM of huperzine A attenuated Aβ25‐35‐induced caspase‐3 activity at 6, 12, 24, and 48 hr posttreatment. Our results provide the first direct evidence that huperzine A protects neurons against Aβ25‐35‐induced apoptosis via the inhibition of ROS formation and caspase‐3 activity. © 2002 Wiley‐Liss, Inc.