Int Neurourol J.  2014 Sep;18(3):115-125. 10.5213/inj.2014.18.3.115.

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

• Kim M
• Shin MS
• Lee JM
• Cho HS
• Kim CJ
• Kim YJ
• Choi HR
• Jeon JW

• KMID: 2232938
• DOI: http://doi.org/10.5213/inj.2014.18.3.115

Abstract

PURPOSE
Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils.
METHODS
Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c.
RESULTS
Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils.
CONCLUSIONS
Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

Keyword

Berberine; Brain ischemia; Short-term memory; Apoptosis; Phosphatidylinositol 3-kinases

MeSH Terms

Apoptosis*
Berberine*
Blotting, Western
Brain Ischemia
Caspase 3
Cytochromes c
DNA Fragmentation
Gerbillinae
Hippocampus
Immunohistochemistry
Memory, Short-Term
Microglia
Neurons
Neuroprotective Agents
Phosphatidylinositol 3-Kinases
Phosphotransferases*
Berberine
Caspase 3
Cytochromes c
Neuroprotective Agents
Phosphatidylinositol 3-Kinases
Phosphotransferases