title: Silibinin protects H9c2 cardiac cells from oxidative stress and inhibits phenylephrine-induced hypertrophy: potential mechanisms.
abstract: Cardiac hypertrophy is the main response of the heart to various extrinsic and intrinsic stimuli, and it is characterized by specific molecular and phenotypic changes. Recent in vitro and in vivo studies indicate the involvement of reactive oxygen species in the hypertrophic response. In this study, silibinin, a plant flavonolignan extracted from milk thistle with potent antioxidant activity, was evaluated for its effects in (a) preventing hydrogen peroxide (H2O2)-induced cellular damage and (b) blocking the phenylephrine-induced hypertrophic response. Using the in vitro model of embryonic rat heart-derived H9c2 cells, we showed that silibinin has a rather safe profile as concentrations up to 200μM did not affect cell viability. Pretreatment of H9c2 cells with silibinin resulted in better protection of H9c2 cells under conditions of H2O2-induced cellular stress compared to untreated cells as indicated by cell viability and DNA fragmentation assays. Furthermore, silibinin attenuated the phenylephrine-induced hypertrophic response as evidenced by the measurement of cell surface, up-regulation of atrial natriuretic peptide and increase of cellular protein levels. Moreover, silibinin repressed the phenylephrine-induced phosphorylation of ERK1/2 kinases, while it appeared to inhibit the weakly activated by phenylephrine phosphorylation of Akt. Based on our results, silibinin may attenuate the phenylephrine-induced hypertrophic response of H9c2 cells via antioxidant mechanisms involving mainly the inhibition of the intracellular signaling pathways mediated by ERK1/2 MAPKs and Akt.
authors: Department of Molecular Biology and Genetics, Democritus University of Thrace, University Campus, Dragana, Alexandroupolis 68100, Greece.
authors: Ioannis
authors: I
authors: Anestopoulos
authors: Anthula
authors: A
authors: Kavo
authors: Ioannis
authors: I
authors: Tentes
authors: Alexandros
authors: A
authors: Kortsaris
authors: Mihalis
authors: M
authors: Panayiotidis
authors: Antigone
authors: A
authors: Lazou
authors: Aglaia
authors: A
authors: Pappa
mesh_terms: D000818:Animals; D000975:Antioxidants; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D053938:DNA Fragmentation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000378:metabolism; D020944:Silybum marianum / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010656:Phenylephrine / Q000009:adverse effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; C574981:PI3KAP protein, rat; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012235:Rhodamines; D012838:Silymarin; D010656:Phenylephrine; C022027:lissamine rhodamine B; D000077385:Silybin; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3