title: Paeoniflorin protects myocardial cell from doxorubicin-induced apoptosis through inhibition of NADPH oxidase.
abstract: Increased intracellular reactive oxygen species (ROS) are involved in doxorubicin (DOX)-induced myocardial cell apoptosis, and paeoniflorin (PEF) has been shown to exert an antioxidant effect. The aim of the present study was to explore the protective effect of PEF on DOX-induced myocardial cell apoptosis and the underlying mechanisms. In cultured H9c2 cells, different concentrations (1, 10, or 100 μmol/L) of PEF was added for 2 h prior to exposure to DOX (5 μmol/L) for 24 h. Cell apoptosis was evaluated by hoechst 33342 staining, and caspase-3 expression and activity. The mRNA and protein expression of NADPH oxidase (NOX) 2 and NOX4 was determined by real-time polymerase chain reaction and Western blot, respectively. Intracellular ROS and NOX activity were measured by assay kit. The results showed that DOX significantly increased myocardial cell apoptosis, increased caspase-3 expression and activity concomitantly with enhanced ROS production, and increased NOX2, NOX4 mRNA and protein expression, and NOX activity. These effects were remarkably inhibited by pretreatment of PEF. Our results suggested that PEF has a protective effect against DOX-induced myocardial cell apoptosis through a mechanism involving a decrease in ROS production by inhibition of NOX2, NOX4 expression, and NOX activity.
authors.affiliation: Department of Pharmacy, Ruikang Hospital, Guangxi University of Traditional Chinese Medicine, Nanning, China.
authors.forename: Jian-Zhe
authors.initials: JZ
authors.lastname: Li
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Yu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wu
authors.forename: Qing-Rui
authors.initials: QR
authors.lastname: Shao
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Dong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D005960:Glucosides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D039821:Monoterpenes; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D006027:Glycosides
chemical_list: D000903:Antibiotics, Antineoplastic; D001565:Benzoates; D001952:Bridged-Ring Compounds; D053148:Caspase 3; D004317:Doxorubicin; D005960:Glucosides; D008562:Membrane Glycoproteins; D039821:Monoterpenes; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C015423:peoniflorin; D006027:Glycosides; C500593:Cybb protein, rat; C498911:Nox4 protein, rat