title: Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway.
abstract: OBJECTIVE
  To determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes.
  
  
  METHODS
  The cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined.
  
  
  RESULTS
  NE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h.
  
  
  CONCLUSIONS
  The present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Xiu-xiu
authors.initials: XX
authors.lastname: Lv
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Yu
authors.forename: Hua-dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Yu-xia
authors.initials: YX
authors.lastname: Yan
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Da-Xiang
authors.initials: DX
authors.lastname: Lu
authors.forename: Ren-Bin
authors.initials: RB
authors.lastname: Qi
authors.forename: Chao-Feng
authors.initials: CF
authors.lastname: Hu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D053143:Caspase 2 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D004247:DNA; D007770:L-Lactate Dehydrogenase; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate; D009638:Norepinephrine