title: Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved.
abstract: Berberine is an alkaloid derived from herb the Berberis sp. and has long-term use in Oriental medicine. Studies along the years have demonstrated its beneficial effect in various neurodegenerative and neuropsychiatric disorders. The subject of this study was to evaluate whether berberine protects against delayed neuronal cell death in organotypic hippocampal culture (OHC) exposed to oxygen and glucose deprivation (OGD) and the cell signaling mechanism related to its effect. Hippocampal slices were obtained from 6 to 8-days-old male Wistar rat and cultured for 14 days. Following, the cultures were exposed for 1h to OGD and then treated with Berberine (10 and 20μM). After 24h recovery, propidium iodide (PI) uptake was analyzed and a decrease was observed in PI uptake on OGD Ber-treated culture, which means a decrease in cellular death. Western blot analysis showed that proteins Akt, GSK3β, ERK and JNK appear to play a role in berberine-mediated neuroprotection. Furthermore, capase-3 activity of OGD Ber-treated culture was diminished by control level in a fluorimetry assay. These findings suggest that berberine-mediated neuroprotection after ischemia involves Akt/GSK3β/ERK 1/2 survival/apoptotic signaling pathway as well as JNK and caspase-3 activity inhibition.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035.003 Porto Alegre, RS, Brazil. Electronic address: elisansp@gmail.com.
authors.forename: Elisa Nicoloso
authors.initials: EN
authors.lastname: Simões Pires
authors.affiliation: Instituto de Bioquímica Médica, UFRJ, Av. Carlos Chagas Filho, 373, 21944-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Rudimar Luiz
authors.initials: RL
authors.lastname: Frozza
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035.003 Porto Alegre, RS, Brazil.
authors.forename: Juliana Bender
authors.initials: JB
authors.lastname: Hoppe
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035.003 Porto Alegre, RS, Brazil.
authors.forename: Bruna de Melo
authors.initials: Bde M
authors.lastname: Menezes
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035.003 Porto Alegre, RS, Brazil.
authors.forename: Christianne Gazzana
authors.initials: CG
authors.lastname: Salbego
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001599:Berberine / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D001599:Berberine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3; D005947:Glucose
keywords: Akt/GSK3β/ERK; Berberine; Caspase-3; JNK; Neuroprotection; Oxygen and glucose deprivation