Effect of Berberine on Cell Survival in the Developing Rat Brain Damaged by MK-801

Abstract

Berberine is an isoquinoline alkaloid isolated from goldenthread, Coptidis Rhizoma and shown to have many biological and pharmacological effects. We previously reported that berberine promotes cell survival and differentiation of neural stem cells. To examine whether berberine has survival promoting effect on damaged neuronal cells, we generated a cellular model under oxidative stress and an neonatal animal model of degenerating brain disease by injecting MK-801. MK801, a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors, acts as a neurotoxin in developing rats by inhibiting NMDA receptors and induce neuronal cell death. We found that the survival rate of the SH-SY5Y cells under oxidative stress was increased by 287% and 344%, when treated with 1.5 and 3.0µg/ml berberine, respectively. In the developing rats injected by MK801, we observed that TUNEL positive apoptotic cells were outspread in entire brain. The cell death was decreased more than 3 fold in the brains of the MK-801-induced neurodegenerative animal model when berberine was treated to the model animals. This suggests that berberine promotes activity dependent cell survival mediated by NMDA receptor because berberine is known to activate neurons by blocking K+ current or lowering the threshold of the action potential. Taken together, berberine has neuroprotective effect on damaged neurons and neurodegenerating brains of neonatal animal model induced by MK-801 administration.

<i>COSCINIUM FENESTRATUM</i> PROTECTS AGAINST ETHANOL-INDUCED NEURODEGENERATION IN ADULT RAT BRAIN

“…However, other effect related to the neuroprotection induced by this plant extract such as anti-apoptotic effect was also reported (Lee et al, 2010). Thus, the neuroprotective effect of CF related to anti-apoptotic effect still could not be excluded.…”

“…It has been reported that berberine attenuated neuronal damage in ischemia/reperfusion model (Yoo et al, 2006) and enhances neuronal cell survival and differentiation in rat's hippocampus (Lim et al, 2008). In addition, CF extract have been previously reported to exhibit the neuroprotective effect via its antioxidant activity leading to the decreased oxidative stress and finally decreased neurodegeneration in neonatal animal model (Lee et al, 2010). These lines of evidence are in agreement with our finding that CF extract used in this study contained berberine and it could decrease neurodegeneration in rat brain induced by ethanol administration.…”

Berberis Vulgaris and Berberine: An Update Review

“…Berberine activates neurons by blocking K + current and lowering the threshold of the action potential. In a neonatal rat model of degenerating brain disease induced by MK‐801, berberine has shown neuroprotective effects on damaged neurons probably via blocking K + current and lowering the threshold of the action potential (Lee et al ., ) adenosine monophosphate (AMP)‐activated protein kinase (AMPK) activation in BV‐2 microglia (Lu et al ., ), reducing the production of tumor necrosis factor‐α, interleukin‐1β, and prostaglandin E2 from activated microglia (Nam et al ., ; Chen et al ., ), inhibition of the excessive production of glutamate (Campisi et al ., ; Lin et al ., ), reducing matrix metalloproteinase‐9 activity (Hong et al ., ), decreasing nitric oxide (NO) production in oligodendroglial cells (Nadjafi et al ., ), increasing heme oxygenase‐1 mRNA and protein expression (Chen et al ., ), and attenuation of intracellular Ca 2+ overload (Nadjafi et al ., ) are other mechanisms proposed for neuroprotective and anti‐neuroinflammatory effects of berberine.…”

Berberine: Pathways to protect neurons

“…In the patch‐clamp perforated whole‐cell recording mode, tetrahydroberberine, hydrogenated form of BBR, blocks membrane K + channels, which contributes to its inhibition of intracellular message‐mediated outward current (J. Wu & Jin, ). In a recent study, BBR probably stimulate cell survival of neuronal cells expressing NMDA receptors by blocking potassium current or lowering the threshold of the action potential in animal model of neonatal brain damaged by NMDA receptor antagonist—MK801 (T. Lee, Heo, & Kim, ). Furthermore, BBR protects against ischemia damage through blockades on transient outward potassium current (IA) and delayed rectifier potassium current (IK) are preferential for IK and in a concentration‐dependent manner in acutely isolated CA1 pyramidal neurons of rat hippocampus (F. Wang et al, ).…”