title: Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2.
abstract: Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H(2)O(2)-induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H(2)O(2) was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in H(2)O(2)-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.
authors.affiliation: VestibuloCochlear Research Center and Department of Microbiology, Iksan, Jeonbuk 570-749, Korea.
authors.forename: Channy
authors.initials: C
authors.lastname: Park
authors.forename: Hong Seob
authors.initials: HS
authors.lastname: So
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Myung Ja
authors.initials: MJ
authors.lastname: Youn
authors.forename: Byung-Soon
authors.initials: BS
authors.lastname: Moon
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Shin
authors.forename: In
authors.initials: I
authors.lastname: Lee
authors.forename: Seong-Keun
authors.initials: SK
authors.lastname: Moon
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one