Cytoprotection against hydrogen peroxide-induced cell death in cultured mouse mesangial cells by erigeroflavanone, a novel compound from the flowers of Erigeron annuus.
Hyperglycemia-induced oxidative stress has been suggested as a mechanism underlying diabetic complications. Oxidative stress triggers cell death in various cell types, including glomerular mesangial cells which play important roles in diabetic nephropathy. In the present study, we investigated the potential cytoprotective effect of erigeroflavanone, a novel flavanone derivative from the flowers of Erigeron annuus, in cultured mouse mesangial cells using hydrogen peroxide (H2O2) as an oxidative stress inducer. Our data show that hydrogen peroxide induced a decrease in cell viability that was attenuated by erigeroflavanone. Hydrogen peroxide treatment increased formation of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). This enhanced ROS formation was significantly reduced by pretreatment with erigeroflavanone in a dose-dependent manner. Hydrogen peroxide treatment also induced phosphorylation of the mitogen-activated protein kinases (MAPKs), c-Jun terminal kinase (JNK), extracellular-regulated kinase (ERK) and p38, and activated caspase-3. Pretreatment with erigeroflavanone inhibited hydrogen peroxide-induced activation of MAPKs and caspase-3. From these data we conclude that erigeroflavanone provides a protective effect against oxidative stress-induced cell death in mesangial cells that is associated with its antioxidant action and inhibition of MAPKs and caspase-3. These results suggest that erigeroflavanone has potential as a therapeutic agent in the treatment of renal diabetic complications.
Kim
Ohn Soon
OS
Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, South Korea.
Kim
Young Sook
YS
Jang
Dae Sik
DS
Yoo
Nam Hee
NH
Kim
Jin Sook
JS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D049919:Erigeron / Q000737:chemistry*; D044950:Flavanones / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases; D050527:Mesangial Cells / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D044950:Flavanones; D017382:Reactive Oxygen Species; C529414:erigeroflavanone; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3