School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
Department of Pharmacy, Changchun University of Chinese Medicine Affiliated Third Clinical Hospital, Changchun, 130117, China.
Biochem Biophys Res Commun. 2022 Sep 10;620:56-62. doi: 10.1016/j.bbrc.2022.06.076. Epub 2022 Jun 25.
The aim of this study was to investigate the antidepressant effect of Jujuboside A (JuA) on corticosterone (CORT)-induced depression in mice and explore the underlying mechanisms.
The mice models were submitted to CORT and treated with JuA (10 and 30 mg/kg) for three weeks. Experiments were also performed on mice with brain-derived neurotrophic factor knockdown (BDNF (±)) as control subjects. Behavioral tests, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM), were then performed to evaluate the antidepressant effect of JuA. The expression levels of BDNF, tyrosine kinase receptor B (TrkB), and cyclic AMP response element binding protein (CREB) in the hippocampi of mice were examined by immunohistochemistry (IHC) and Western blot. The effect of JuA on the viability of mouse hippocampal cells (HT22) was also assessed by CCK-8 assay.
JuA significantly decreased the OFT and TST immobility time of the mice, the total distance travelled and the time spent in the central area also effectively increased in the OFT. In the MWM, the escape latencies of the mice decreased remarkably, while the number of times the mice crossed the platform and the target quadrant increased significantly after treatment with JuA. In addition, the BDNF, TrkB, and CREB expression levels were significantly increased in the hippocampi of the mice treated with JuA. Furthermore, JuA clearly attenuated CORT-induced cell injury, as evidenced by the increased viability of the HT22 cells.
These findings demonstrated that JuA may exhibit potential antidepressant effect in mice by increasing protein expression levels of BDNF, TrkB, CREB, and improving the viability of the hippocampal cells.
本研究旨在探讨酸枣仁皂甙 A(JuA)对皮质酮(CORT)诱导的抑郁小鼠的抗抑郁作用及其机制。
采用 CORT 造模并给予 JuA(10 和 30mg/kg)处理 3 周,以 BDNF 敲低(BDNF(±))小鼠作为对照。通过旷场实验(OFT)、悬尾实验(TST)、强迫游泳实验(FST)和 Morris 水迷宫(MWM)实验评估 JuA 的抗抑郁作用,免疫组化(IHC)和 Western blot 检测小鼠海马 BDNF、酪氨酸激酶受体 B(TrkB)和环磷酸腺苷反应元件结合蛋白(CREB)的表达水平,CCK-8 法检测 JuA 对小鼠海马细胞(HT22)活力的影响。
JuA 显著降低了小鼠的 OFT 和 TST 不动时间,OFT 中总距离和中央区域时间也明显增加;MWM 中,逃避潜伏期明显降低,而经过 JuA 处理后,穿过平台的次数和目标象限时间明显增加。此外,JuA 还显著增加了小鼠海马 BDNF、TrkB 和 CREB 的表达水平。此外,JuA 明显减轻了 CORT 诱导的细胞损伤,HT22 细胞活力明显增加。
这些发现表明,JuA 可能通过增加 BDNF、TrkB、CREB 蛋白表达水平和改善海马细胞活力,在小鼠中表现出潜在的抗抑郁作用。