Effect of Cryptotanshinone on Measures of Rat Cardiomyocyte Oxidative Stress and Gene Activation Associated with Apoptosis

Abstract

<b><i>Background:</i></b> Oxidative stress is a key factor that results in cardiomyocyte apoptosis and cardiovascular diseases. Cryptotanshinone (CTS), one of the major bioactive constitutes extracted from the root of the plant <i>Salvia miltiorrhiza</i>Bunge, has been widely studied for various disease treatments. However, the roles of CTS on cardiomyocytes remain unclear. <b><i>Methods:</i></b> In the present study, neonatal rat cardiomyocytes were pretreated with CTS for 4 h before being exposed to H₂O₂. Cell viability for the cells with or without pretreatment with CTS before exposure to H₂O₂ was evaluated by the MTT assay. Production of lactate dehydrogenase (LDH), nitric oxide (NO), prostaglandin E₂ (PGE₂), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxides (GSH-Px) was quantified by corresponding detection kits. The mRNA levels of Bcl-2 antiapoptotic and Bax-like proapoptotic genes were quantified with RT-PCR. Production of reactive oxygen species (ROS) was qualified and quantified with a dichlorofluorescein diacetate cellular ROS detection assay kit. The extracellular signal-related kinase (ERK) phosphorylation and nuclear factor κB (NF-κB) activation were measured by Western blot. <b><i>Results:</i></b> Our results revealed that the CTS pretreatment could enhance cell viability and promote Bcl-2 antiapoptotic gene expression. Additionally, CTS could abolish the H₂O₂-induced production of NO, LDH, and PGE₂. Consistent with these findings, CTS could inhibit ROS and MDA production and promote SOD, CAT, and GSH-Px activities. Mechanistically, CTS may achieve these processes by inhibiting ERK and NF-κB signal pathways. <b><i>Conclusion:</i></b> CTS protects cardiomyocytes against the H₂O₂-induced cellular injuries through ERK and NF-κB inactivation and ROS scavenging. Therefore, CTS is a promising reagent against ROS-induced cardiomyopathy.