Department of Cardiology, Affiliated Hospital 2 of Nantong University, Nantong, China.
Department of Pharmacology, Pharmacy College, Nantong University, Nantong, China.
Brain Behav. 2022 Aug;12(8):e2705. doi: 10.1002/brb3.2705. Epub 2022 Jul 18.
The most striking feature of depression is sadness and a loss of interest in activities, which represents a major cause of disability globally. Therefore, it is necessary to identify novel antidepressants for clinical practice. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides that can be extracted from Panax ginseng and has been demonstrated to improve both memory and learning. The purpose of this study was to provide broad insight into the mechanisms underlying depression and gain greater insights into antidepressant therapy.
In this study, we first established an effective and feasible depression animal model of chronic unpredictable mild stress (CUMS) and behavioral testing was evaluated by the forced swim test (FST), the tail suspension test (TST) and the sucrose preference test. Following pretreatment with Rh2 (10 and 20 mg/kg), the immobility time of mice was reduced without affecting locomotor activity in both the FST and TST. Western blotting and immunofluorescence were used to investigate the activation of the hippocampal BDNF signaling pathway and hippocampal neurogenesis.
Different concentrations of Rh2 significantly reduced depressive-like symptoms in CUMS-induced mice and downregulated the effects of the BDNF signaling cascade and neurogenesis in the hippocampus. Furthermore, the administration of K252a completely prevented the antidepressant-like activity of Rh2 in mice.
The results indicated that Rh2 possesses the antidepression action via the positive regulation of the BDNF-TrkB pathway.
抑郁症最显著的特征是悲伤和对活动失去兴趣，这是全球致残的主要原因之一。因此，有必要为临床实践寻找新型抗抑郁药。人参皂苷 Rh2（Rh2）是从人参中提取的主要生物活性人参皂苷之一，已被证明可以改善记忆力和学习能力。本研究旨在为抑郁症的发病机制提供更广泛的认识，并深入了解抗抑郁治疗。
本研究首先建立了慢性不可预测轻度应激（CUMS）的有效可行的抑郁症动物模型，并通过强迫游泳试验（FST）、悬尾试验（TST）和蔗糖偏好试验评估行为测试。用 Rh2（10 和 20mg/kg）预处理后，FST 和 TST 中，小鼠的不动时间减少，而不影响运动活性。Western blotting 和免疫荧光用于研究海马 BDNF 信号通路和海马神经发生的激活。
不同浓度的 Rh2 可显著减轻 CUMS 诱导的小鼠抑郁样症状，并下调海马 BDNF 信号级联和神经发生的作用。此外，K252a 的给药完全阻止了 Rh2 在小鼠中的抗抑郁样作用。
结果表明，Rh2 通过正向调节 BDNF-TrkB 通路发挥抗抑郁作用。
