title: Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle cells via the inhibition of ROS generation and NF-kappaB activation.
abstract: Plantainoside D (PD), was isolated from the leaves of Picrorhiza scrophulariiflora (Scrophulariaceae). The anti-oxidative activity of PD was evaluated based on scavenging effects on hydroxyl radicals and superoxide anion radicals. Adriamycin (ADR) is a potent anti-tumor drug known to cause severe cardiotoxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity has not been understood. This study was undertaken to investigate the protective effect of PD against ADR-induced apoptosis. In vitro, ADR caused dose-dependent toxicity in H9c2 cardiac muscle cells. Pre-treatment of the cardiac muscle cells with PD significantly reduced ADR-induced apoptosis of cardiac muscle cells. PD inhibited the ROS produced by ADR in the cardiac muscle cells. As well, PD increased GSH(glutathione), compared with ADR. In response to ADR, NF-kappaB was activated in H9c2 cells. However the treatment of PD reduced the activation of NF-kappaB. We also observed that the NF-kappaB inhibitor, PDTC, inhibited the cytotoxic effect on ADR-induced apoptosis in cardiac muscle cells. In parallel, IkappaBalpha-dominant negative plasmid-overexpression abrogated ADR-induced apoptosis in H9c2 cardiac muscle cells. In conclusion, these results suggest that Plantaionoside D can inhibit ADR-induced apoptosis in H9C2 cardiac muscle cells via inhibition of ROS generation and NF-kappaB activation. The pure compound PD can be a potential candidate agent which protects cardiotoxicity in ADR-exposed patients.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju, Chonbuk 560-180, Republic of Korea.
authors.forename: Do-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Ki-Chan
authors.initials: KC
authors.lastname: Ha
authors.forename: Geum-Hwa
authors.initials: GH
authors.lastname: Lee
authors.forename: Seong-Tshool
authors.initials: ST
authors.lastname: Hong
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Yong-Keun
authors.initials: YK
authors.lastname: Jung
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D004187:Disaccharides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D028083:Scrophulariaceae / Q000737:chemistry*; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D003373:Coumaric Acids; D004187:Disaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C516918:plantainoside D; C066229:prolinedithiocarbamate; D004317:Doxorubicin; D011392:Proline; D005978:Glutathione