Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons

SCOPE: Thymoquinone (TQ) has been used as a potential therapeutic for diseases such as cancer and diabetes. Herein, we aim to investigate the effect of TQ on behavioral and molecular parameters in healthy rat hippocampus. METHODS: TQ (20 mg kg-1  d-1 ) is administered intragastrically for 15 days to adult rats. After behavioral tests, the hippocampal tissues are investigated at the histological and molecular levels. RESULTS: In both dentate gyrus and cornu ammonis 1, TQ significantly increases the number of hippocampal neurons. This increase is supported by a significant increase in the doublecortin expression on both gene and protein levels. In addition, TQ significantly decreases the amount of Caspase-3 expression and the cleavage of poly ADP ribose polymerase, indicating a decrease in apoptosis. Further, ERK, GSK-3, JNK, CREB, and iNOS proteins are found to be positively regulated by TQ. However, the gene expression of synapsin, synaptophysin, NGF, AKT, Bax, NFkB, and p53 and the protein expression of BDNF and nNOS are not affected by TQ. CONCLUSION: These findings suggest that TQ has an enhancing effect on cell survival and neurogenesis in healthy hippocampus, rather inducing apoptosis in damaged neurons. This may proceed via ERK/JNK and CREB signaling pathways as a candidate acting mechanism for TQ.