PMID- 25279238 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20141003 LR - 20211021 IS - 2093-4777 (Print) IS - 2093-6931 (Electronic) IS - 2093-4777 (Linking) VI - 18 IP - 3 DP - 2014 Sep TI - Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway. PG - 115-25 LID - 10.5213/inj.2014.18.3.115 [doi] AB - 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. FAU - Kim, Mia AU - Kim M AD - Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Oriental Medicine, Kyung Hee University, Seoul, Korea. FAU - Shin, Mal Soon AU - Shin MS AD - Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Lee, Jae Min AU - Lee JM AD - Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Cho, Han Sam AU - Cho HS AD - Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Kim, Chang Ju AU - Kim CJ AD - Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Kim, Young Joon AU - Kim YJ AD - Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Choi, Hey Ran AU - Choi HR AD - Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul, Korea. FAU - Jeon, Jung Won AU - Jeon JW AD - Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea. LA - eng PT - Journal Article DEP - 20140924 PL - Korea (South) TA - Int Neurourol J JT - International neurourology journal JID - 101534513 PMC - PMC4180161 OTO - NOTNLM OT - Apoptosis OT - Berberine OT - Brain ischemia OT - Phosphatidylinositol 3-kinases OT - Short-term memory COIS- The authors report no potential conflict of interest relevant to this article. EDAT- 2014/10/04 06:00 MHDA- 2014/10/04 06:01 PMCR- 2014/09/01 CRDT- 2014/10/04 06:00 PHST- 2014/09/09 00:00 [received] PHST- 2014/09/17 00:00 [accepted] PHST- 2014/10/04 06:00 [entrez] PHST- 2014/10/04 06:00 [pubmed] PHST- 2014/10/04 06:01 [medline] PHST- 2014/09/01 00:00 [pmc-release] AID - 10.5213/inj.2014.18.3.115 [doi] PST - ppublish SO - Int Neurourol J. 2014 Sep;18(3):115-25. doi: 10.5213/inj.2014.18.3.115. Epub 2014 Sep 24.