title: Inhibition of NADPH Oxidase Mediates Protective Effect of Cardiotonic Pills against Rat Heart Ischemia/Reperfusion Injury.
abstract: Cardiotonic pill (CP) is a compound Chinese medicine currently used in China for treatment of ischemic angina pectoris. Our previous results indicated that a single dosing of CP pretreatment at 0.8 g/kg attenuates ischemia/reperfusion- (I/R-) induced myocardial injury and cardiac microcirculatory disturbance. The present study aimed to investigate the effect of CP at low dosage in a multiple dosing manner and to uncover the mechanism of antioxidative activity of CP. Male Sprague-Dawley rats were subjected to left anterior descending artery occlusion for 30 min followed by 60 min reperfusion. CP was administrated daily by gavage for six days at 0.1, 0.4, and 0.8 g/kg/day before I/R. Results showed that multiple dosing of CP at three doses significantly reduced I/R-induced myocardial injury, microcirculatory disturbance, and oxidative stress. CP dramatically inhibited I/R-induced nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase subunit gp91(phox) expression and p67(phox) and p47(phox) translocation from cytosol to cell membrane. Translocation of cytosolic subunits to membrane is required for the activation of NADPH oxidase. These data suggested that multiple dosing of CP at doses ranging from 0.1 to 0.8 g/kg/day reduced I/R-induced rat myocardial injury and microcirculatory disturbance, which was mediated by inhibition of NADPH oxidase activation.
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing 100191, China ; Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han