TY - JOUR
T1 - Baicalein Preventive Treatment Confers Optimal Cardioprotection by PTEN/Akt/NO Activation
AU - Li, Jing
AU - Chang, Wei Tien
AU - Li, Chang Qing
AU - Lee, Chunpei
AU - Huang, Hsien Hao
AU - Hsu, Chin Wan
AU - Chen, Wen Jone
AU - Zhu, Xiangdong
AU - Wang, Chong Zhi
AU - Vanden Hoek, Terry L.
AU - Shao, Zuo Hui
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Baicalein is a flavonoid with excellent oxidant scavenging capability. It has been reported to protect against a variety of oxidative injuries including ischemia/reperfusion (I/R). However, the optimal treatment strategy for I/R injury and the protective mechanisms are not fully understood. In this study we employed an established chick cardiomyocyte model of I/R and investigated the effects of three baicalein treatment strategies on reactive oxygen species (ROS) scavenging, nitric oxide (NO) production and cell viability. The molecular signaling pathways were also explored. Compared to the I/R control (cell death 52.2±2.0%), baicalein preventive treatment (25μM, pretreated for 72h and continued through I/R) conferred the best protection (19.5±3.9%, p<0.001), followed by I/R treatment (treated during I/R) and reperfusion treatment (treated at reperfusion only). Preventive and I/R treatments almost completely abolished ROS generation during both ischemic and reperfusion phases, and increased NO production and Akt phosphorylation. Reperfusion treatment reduced the ROS burst in the early reperfusion phase only, and had no effect on NO production and Akt activation. Further, the phosphorylation of phosphatase and tensin homolog (PTEN), a phosphatase negatively regulating Akt activation, was significantly increased by baicalein preventive treatment and slightly by the I/R treatment. PTEN protein expression was reduced in the same trend accordingly. Baicalein reperfusion treatment had no effects on PTEN phosphorylation and expression. Our results indicate that baicalein preventive treatment confers optimal cardioprotection against I/R injury, and this protection involves effective oxidant scavenging and the activation of PTEN/Akt/NO pathway.
AB - Baicalein is a flavonoid with excellent oxidant scavenging capability. It has been reported to protect against a variety of oxidative injuries including ischemia/reperfusion (I/R). However, the optimal treatment strategy for I/R injury and the protective mechanisms are not fully understood. In this study we employed an established chick cardiomyocyte model of I/R and investigated the effects of three baicalein treatment strategies on reactive oxygen species (ROS) scavenging, nitric oxide (NO) production and cell viability. The molecular signaling pathways were also explored. Compared to the I/R control (cell death 52.2±2.0%), baicalein preventive treatment (25μM, pretreated for 72h and continued through I/R) conferred the best protection (19.5±3.9%, p<0.001), followed by I/R treatment (treated during I/R) and reperfusion treatment (treated at reperfusion only). Preventive and I/R treatments almost completely abolished ROS generation during both ischemic and reperfusion phases, and increased NO production and Akt phosphorylation. Reperfusion treatment reduced the ROS burst in the early reperfusion phase only, and had no effect on NO production and Akt activation. Further, the phosphorylation of phosphatase and tensin homolog (PTEN), a phosphatase negatively regulating Akt activation, was significantly increased by baicalein preventive treatment and slightly by the I/R treatment. PTEN protein expression was reduced in the same trend accordingly. Baicalein reperfusion treatment had no effects on PTEN phosphorylation and expression. Our results indicate that baicalein preventive treatment confers optimal cardioprotection against I/R injury, and this protection involves effective oxidant scavenging and the activation of PTEN/Akt/NO pathway.
KW - Akt
KW - Baicalein
KW - Cardiomyocyte
KW - Ischemia/Reperfusion
KW - Nitric Oxide
KW - PTEN
KW - Reactive Oxygen Species
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UR - http://www.scopus.com/inward/citedby.url?scp=85026520529&partnerID=8YFLogxK
U2 - 10.1142/S0192415X17500525
DO - 10.1142/S0192415X17500525
M3 - Article
C2 - 28760044
AN - SCOPUS:85026520529
SN - 0192-415X
VL - 45
SP - 987
EP - 1001
JO - American Journal of Chinese Medicine
JF - American Journal of Chinese Medicine
IS - 5
ER -