Berberine Attenuates Axonal Transport Impairment and Axonopathy Induced by Calyculin A in N2a Cells

作者：Xiaofeng Liu, Jie Zhou, Morad Dirhem Naji Abid, Huanhuan Yan, Hao Huang, Limin Wan, Zuo‐Hua Feng, Juan Chen · 发表于：PLoS ONE · 年份：2014 · DOI：10.1371/journal.pone.0093974 · 被引用次数：34 · 研究领域：Berberine and alkaloids research、Alkaloids: synthesis and pharmacology、Alzheimer's disease research and treatments

Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD.