Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
Mol Nutr Food Res. 2018 Mar;62(5). doi: 10.1002/mnfr.201700768. Epub 2018 Feb 12.
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.
TQ (20 mg kg d ) is administered intragastrically for 15 days to adult rats. After behavioral tests, the hippocampal tissues are investigated at the histological and molecular levels.
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.
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.
百里醌（TQ）已被用作癌症和糖尿病等疾病的潜在治疗方法。在此，我们旨在研究 TQ 对健康大鼠海马体行为和分子参数的影响。
TQ（20mg/kg/d）通过灌胃给药，连续给药 15 天。在行为测试后，在组织学和分子水平上研究海马组织。
在齿状回和角状回 1 中，TQ 显著增加海马神经元的数量。这种增加得到了双重皮质蛋白在基因和蛋白水平表达的显著增加的支持。此外，TQ 显著降低了 Caspase-3 的表达量和多聚 ADP 核糖聚合酶的切割，表明细胞凋亡减少。此外，ERK、GSK-3、JNK、CREB 和 iNOS 蛋白被发现被 TQ 正向调节。然而，突触素、突触小泡蛋白、NGF、AKT、Bax、NFkB 和 p53 的基因表达以及 BDNF 和 nNOS 的蛋白表达不受 TQ 影响。
这些发现表明，TQ 对健康海马体中的细胞存活和神经发生具有增强作用，而不是诱导受损神经元凋亡。这可能通过 ERK/JNK 和 CREB 信号通路作为 TQ 的候选作用机制。
