title: Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia.
abstract: Berberine, a primary pharmacological active constitute of Coptidis Rhizoma, could inhibit neuronal apoptosis in cerebral ischemia. Here, we aimed to investigate whether and how HIF-1 is implicated in the anti-apoptosis effect of berberine on neurons under hypoxia/ischemia. Viability of PC12 cells treated with berberine prior to or following CoCl2-induced hypoxia was evaluated. Annexin V-PI staining was employed to analyse cell apoptosis ratio. HIF-1α and apoptosis-associated molecules were detected via Western blotting. TUNEL and immunohistochemistry were used to demonstrate apoptosis, HIF-1α and p53 levels in cerebral tissue of middle cerebral artery occlusion (MCAO) rats. Berberine pretreatment promoted PC12 cells survival and inhibited apoptosis under hypoxia condition. At the same time, it decreased cell viability and enhancement of apoptosis were observed with berberine treatment under hypoxia. Decreased HIF-1α, caspase 9, caspase 3 and increased Bcl-2/Bax ratio were responsible for the anti-apoptosis of berberine pretreatment. However, pro-apoptosis by berberine under hypoxia was indicated with opposing regulation of those molecules. Significant reduction of apoptosis, HIF-1α and p53 were found in cerebral tissue of MCAO rats treated with berberine. The present study suggests that berberine regulates neuronal apoptosis in cerebral ischemia, which might be dependent on the degree of cell injury. HIF-1 and the followed apoptotic pathway are involved in those effects of berberine.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Qian
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003035:Cobalt / Q000494:pharmacology; D000089042:Coptis chinensis; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; C494828:Bax protein, rat; D004365:Drugs, Chinese Herbal; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001599:Berberine; D003035:Cobalt; C107393:Coptidis rhizoma extract; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; C018021:cobaltous chloride