Protective Effect of Isorhynchophylline Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

• Published in: Cellular and molecular neurobiology 2012-04, Vol.32 (3), p.353-360
• Main Authors: Xian, Yan-Fang, Lin, Zhi-Xiu, Mao, Qing-Qiu, Ip, Siu-Po, Su, Zi-Ren, Lai, Xiao-Ping
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - toxicity; Animals; Apoptosis; BAX protein; Bcl-2 protein; Biomedical and Life Sciences; Biomedicine; Caspase-3; Cell Biology; Cell viability; DNA fragmentation; Glutathione; Indole Alkaloids - pharmacology; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Membrane Potential, Mitochondrial - physiology; Neurobiology; Neurodegenerative diseases; Neuromodulation; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Neurotoxicity; Original Research; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Oxindoles; PC12 Cells; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - toxicity; Pheochromocytoma cells; Rats; Reactive oxygen species; Senile plaques; β-Amyloid
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-011-9763-5

Beta-amyloid peptide (Aβ), a major protein component of senile plaques, has been considered as a critical cause in the pathogenesis of Alzheimer’s disease (AD). Modulation of the Aβ-induced neurotoxicity has emerged as a possible therapeutic approach to ameliorate the onset and progression of AD. The present study aimed to evaluate the protective effect of isorhynchophylline, an oxindole alkaloid isolated from a Chinese herb Uncaria rhynchophylla, on Aβ-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in Aβ 25-35 -treated PC12 cells. In addition, isorhynchophylline significantly suppressed the formation of DNA fragmentation and the activity of caspase-3 and moderated the ratio of Bcl-2/Bax. These results indicate that isorhynchophylline exerts a neuroprotective effect against Aβ 25-35 -induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and suppressing the mitochondrial pathway of cellular apoptosis.