Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E)-2,6-Bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH)

International Journal of Molecular Sciences

Gui-Zhen Ao¹  Xiao-Jing Chu¹  Yuan-Yuan Ji¹ 

[1] College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China;

关键词: curcumin analogue;    free radical scavenger;    hydrogen peroxide;    PC12 cells;    apoptosis;   

DOI  :  10.3390/ijms15033970

来源: mdpi

【 摘 要 】

The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H₂O₂ damage. MCH displayed superior O₂^•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 μM H₂O₂ caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 μM before H₂O₂ exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H₂O₂. These results show that MCH protects PC12 cells from H₂O₂ injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland