Baicalein protects cardiomyocytes against mitochondrial oxidant injury associated with JNK inhibition and mitochondrial Akt activation.
Baicalein, a flavonoid derived from Scutellaria baicalensis Georgi, possesses cardioprotection against oxidant injury by scavenging reactive oxygen species (ROS). Few studies investigate whether baicalein protection is mediated by attenuating mitochondrial ROS and modulating the prosurvival and proapoptotic signaling. Primary cultured chick cardiomyocytes were used to study the role of baicalein in mitochondrial superoxide [Formula: see text] generation and signaling of Akt and JNK. Cells were exposed to H 2 O 2 for 2 h and baicalein was given 2 h prior to and during 2 h of H 2 O 2 exposure. Cell viability was assessed by propidium iodide and DNA fragmentation. H 2 O 2 (500 μM) significantly induced 45.3 ± 6.2% of cell death compared to the control (p < 0.001) and resulted in DNA laddering. Baicalein (10, 25 or 50 μM) dose-dependently reduced the cell death to 38.7 ± 5.6% (p = 0.226); 31.2 ± 3.9% (p < 0.01); 30.3 ± 5.3% (p < 0.01), respectively. It also attenuated DNA laddering. Further, baicalein decreased intracellular ROS and mitochondrial [Formula: see text] generation that was confirmed by superoxide dismutase PEG-SOD and mitochondria electron transport chain complex III inhibitor stigmatellin. In addition, baicalein increased Akt phosphorylation and decreased JNK phosphorylation in H 2 O 2-exposed cells. Moreover, baicalein augmented mitochondrial phosphorylation of Akt Thr308 and GSK3β Ser9, and prevented mitochondrial cytochrome c release assessed by cellular fractionation. Our results suggest that baicalein cardioprotection may involve an attenuation of mitochondrial [Formula: see text] and an increase in mitochondrial phosphorylation of Akt and GSK3β while decreasing JNK activation.
Department of Emergency Medicine, Center for Cardiovascular Research, University of Illinois Hospital and Health Sciences System, Chicago, IL 60612, USA , Department of Emergency Medicine, Taipei Veterans General Hospital and Emergency Medicine, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsien-Hao
HH
Huang
Zuo-Hui
ZH
Shao
Chang-Qing
CQ
Li
Terry L
TL
Vanden Hoek
Jing
J
Li
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D031364:Scutellaria baicalensis / Q000737:chemistry; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D002316:Cardiotonic Agents; D044950:Flavanones; D017382:Reactive Oxygen Species; D013481:Superoxides; C006680:baicalein; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; D048670:MAP Kinase Kinase 4