Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells.
A number of studies indicate that free radicals are involved in the neurodegeneration in Alzheimer's disease (AD). The present study was mainly conducted to examine the effect of Huperzine B on H(2)O(2) induced toxicity in rat pheochromocytoma line PC12 by measuring cell lesion, level of lipid peroxidation and antioxidant enzyme activities. Following a 30 min exposure of the cells to H(2)O(2) (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with huperzine B (10-100 microM) prior to H(2)O(2) exposure significantly elevated the cell survival, antioxidant enzyme activities and decreased the level of MDA. The above-mentioned neuroprotective effects are also observed with tacrine (1 microM), donepezil (10 microM) and galanthamine (10 microM), suggesting that the neuroprotective effects of cholinesterase inhibitor might partly contribute to the clinical efficacy in AD treatment.
Zhang
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State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 294 Tai-yuan Road, 200031, PR, Shanghai, China.
Tang
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XC
D000110:Acetylcholinesterase / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016716:PC12 Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051381:Rats
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D005609:Free Radicals; C053016:huperzine B; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000110:Acetylcholinesterase