Effect of astragaloside IV against rat myocardial cell apoptosis induced by oxidative stress via mitochondrial ATP-sensitive potassium channels.
Astragaloside is one of the most common traditional Chinese medicines and is derived from Astragalus membranaceus. Astragaloside IV (AsIV) is a monomer located in an extract of astragaloside. The current study investigated the protective effects of AsIV against hydrogen peroxide (H2O2)-induced injury in cardiocytes and elucidated the mechanisms responsible for this protective effect. Cultured neonatal rat cardiocytes were divided into five experimental groups as follows: i) Dimethyl sulfoxide; ii) H2O2; iii) AsIV+H2O2; iv) AsIV+H2O2+5-hydroxydecanoate (5-HD); and v) nicorandil+H2O2. Cardiocyte survival was analyzed using an MTT assay. Lactate dehydrogenase (LDH) release was also assessed to evaluate the viability of the cells. Intracellular reactive oxygen species (ROS) were measured by 2,7-dichlorodihydrofluorescein diacetate staining. The apoptotic rate was measured by flow cytometry. Mitochondrial membrane potential (ΔΨm) and intracellular calcium were observed using a laser confocal microscopy system. The results indicated that AsIV promoted the survival of cardiocytes (P<0.05), attenuated LDH release (P<0.05), ROS production (P<0.01) and apoptosis (P<0.01), stabilized the ΔΨm and reduced intracellular calcium overload (P<0.01) compared with the H2O2 group. The mitochondrial adenosine triphosphate-sensitive potassium channel (mitoKATP) inhibitor 5-HD was observed to partially reverse the protective effect of AsIV. Following treatment with 5-HD, the survival of cardiocytes was reduced (P<0.05), LDH release (P<0.01) and ROS production (P<0.05) were stimulated, ΔΨm and intracellular calcium change were increased (P<0.01) and apoptosis was increased (P<0.01) compared with the AsIV+H2O2 group. Thus, AsIV has potential for use in the suppression of apoptosis resulting from H2O2 exposure, and mitoKATP activation may underlie this protective mechanism.
Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Feng-Ying
FY
Guan
Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Shi-Jie
SJ
Yang
Department of Pediatric Cardiology, Institute of Pediatrics, The First Affiliated Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Jinxiang
J
Liu
Department of Pediatric Cardiology, Institute of Pediatrics, The First Affiliated Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Si-Rui
SR
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D027885:Astragalus propinquus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003652:Decanoic Acids / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000633:toxicity; D006880:Hydroxy Acids / Q000633:toxicity; D008516:Medicine, Chinese Traditional; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D015221:Potassium Channels / Q000378:metabolism*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; C117780:mitochondrial K(ATP) channel; C052064:astragaloside A; C052853:5-hydroxydecanoic acid; D006861:Hydrogen Peroxide