title: Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Mia
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Mal Soon
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Han Sam
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Chang Ju
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Hey Ran
authors.initials: HR
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Jeon
keywords: Apoptosis; Berberine; Brain ischemia; Phosphatidylinositol 3-kinases; Short-term memory