Kobophenol A inhibits sodium nitroprusside-induced cardiac H9c2 cell death through suppressing activation of JNK and preserving mitochondrial anti-apoptotic Bcl-2 and Mcl-1.
Sodium nitroprusside (SNP) releases nitric oxide (NO), a powerful vasodilator, and thus widely used in intensive care unit for treating hypertension emergency. However, cardiac toxicity after SNP administration is a clinical problem. For finding a natural compound that suppressing SNP-induced cardiac toxicity, we tested the protective potential of kobophenol A (Kob A), purified from the root of Caragana sinica, against the toxic effects of SNP. The severe cardiac H9c2 cell death was induced by SNP (2 mM) treatment. Kob A ameliorated SNP-induced cardiac H9c2 cell death, and this protective effect of Kob A may be related to the inhibition of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase activation following SNP administration. In addition, the downregulation of cellular Bcl-2 and Mcl-1 levels by SNP exposure was strongly abrogated in the presence of Kob A. These biological properties of Kob A might provide insights into developing new cardioprotectant against SNP-induced cardiac cell death.
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Department of Health Sciences and Technology, Inje University.
Sung Ryul
SR
Lee
Jong Hwan
JH
Kwak
Su Jin
SJ
Noh
Julius Ryan
JR
Pronto
Kyung Soo
KS
Ko
Byoung Doo
BD
Rhee
Zhelong
Z
Xu
Nari
N
Kim
Jin
J
Han
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D032602:Caragana / Q000737:chemistry / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D013267:Stilbenes / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; C510380:kobophenol A; D009599:Nitroprusside; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3