Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Int J Mol Sci. 2023 Jul 4;24(13):11088. doi: 10.3390/ijms241311088.
Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of and in the 6-OHDA-treated SH-SY5Y cells. Additionally, the inhibitor attenuated the effect of DT on and reduced the cell viability. The DT and activators activated and , and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.
丹参被广泛用于治疗中枢神经系统疾病。我们研究了二氢异丹参酮 I（DT）的作用，DT 是从丹参中提取的一种化合物，以及它在基于体外的 6-羟多巴胺（6-OHDA）诱导的帕金森病（PD）模型中的相应机制。将 SH-SY5Y 人神经母细胞瘤细胞系用 6-羟多巴胺（6-OHDA）预处理，并与 DT 一起孵育。然后分析细胞活力以及活性氧（ROS）和半胱天冬酶-3（caspase-3）的水平。使用实时定量聚合酶链反应测量 DT 对 6-OHDA 处理的 SH-SY5Y 细胞的影响以及核心生物钟基因的表达。我们的结果表明，DT 可减轻 6-OHDA 诱导的 SH-SY5Y 细胞死亡，并抑制 ROS 和 caspase-3。此外，DT 逆转了 6-OHDA 处理的 SH-SY5Y 细胞中 和 的 RNA 和蛋白水平。此外， 抑制剂减弱了 DT 对 和降低细胞活力的作用。DT 和 的激活剂激活 和 ，然后减少 6-OHDA 损伤的 SH-SY5Y 细胞的死亡。DT 增强 SIRT1 沉默，导致 BMAL1 下调和细胞活力降低。总之，我们的研究表明 DT 通过降低 ROS 来减少细胞凋亡，包括抗氧化作用，并通过增强 SIRT1 和抑制 BMAL1 来调节生物钟基因。DT 将来可能对 PD 具有新的治疗潜力，但仍需要进一步的体内研究。
