Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation

• Main Authors: Zuohui Shao, Sy-Jou Chen, Xiangdong Zhu, Chunpei Lee, Hsien-Hao Huang, Angelo Meliton, Changqing Li, Terry L. Vanden Hoek, Jing Li
• Format: Article
• Language: English
• Published: MDPI AG 2018-03-01
• Series: International Journal of Molecular Sciences
• Subjects: intraischemic cooling; delayed cooling; baicalein; ischemia/reperfusion; reactive oxygen species (ROS); cardiomyocyte; Akt; cell death; contractility
• Online Access: http://www.mdpi.com/1422-0067/19/4/973

Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its cardioprotection is diminished when delay in reaching the target temperature occurs. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis Georgi, possesses antioxidant properties. Therefore, we hypothesized that baicalein can rescue cooling cardioprotection when cooling is delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used to assess cell survival and contractility, respectively. Cooling (32 °C) was initiated either during ischemia or during reperfusion. Cell viability and ROS generation were measured. Cell contractility was evaluated by real-time phase-contrast imaging. Our results showed that cooling reduced cell death and ROS generation, and this effect was diminished when cooling was delayed. Baicalein (25 µM), given either at the start of reperfusion or start of cooling, resulted in a comparable reduction of cell death and ROS production. Baicalein improved phospholamban phosphorylation, contractility recovery, and cell survival. These effects were Akt-dependent. In addition, no synergistic effect was observed with the combined treatments of cooling and baicalein. Our data suggest that baicalein may serve as a novel adjunct therapeutic strategy for SCA resuscitation.