Major depressive disorder (MDD) is one of the most common psychiatric disorders. However, the effective drugs for MDD have not yet been developed. WS6 is originally designed with a similar structure as Resveratrol and Pterostilbene. The present study aims to investigate the neuroprotective and ameliorating effects of WS6 treatment in a rat model of chronic unpredictable mild stress (CUMS) induced depression. The results show that CUMS is effective in producing depressive-like behavior in rats as indicated by decreased responses in the locomotor activity, sucrose preference test and increased immobility time. However, WS6 treatment significantly ameliorated these behavioral alterations associated with CUMS-induced depression. Moreover, the reduction in neurogenesis, GABAergic neurons, dendrite complexity, spine density and synaptic plasticity-associate protein 95 (PSD95) by CUMS can be reversed by treatment with WS6. Taken together, this study highlights the neuroprotective and antidepressant-like effects of WS6 against CUMS-induced depression, and suggest a possible mechanism for this protection via changes in neurogenesis within the hippocampus. These finding reveal the therapeutic protection of WS6 for use in clinical trials in the treatment of neuronal deterioration in MDD.

重度抑郁症（MDD）是最常见的精神疾病之一。然而，目前尚未开发出治疗 MDD 的有效药物。WS6 最初设计的结构与白藜芦醇和紫檀芪相似。本研究旨在研究 WS6 治疗在慢性不可预测轻度应激 (CUMS) 诱导的抑郁症大鼠模型中的神经保护和改善作用。结果表明 CUMS 可有效地在大鼠中产生抑郁样行为，如运动活动反应降低、蔗糖偏好测试和不动时间增加所表明的。然而，WS6 治疗显着改善了这些与 CUMS 诱发的抑郁症相关的行为改变。此外，神经发生、GABA 能神经元、树突复杂性的减少，用 WS6 治疗可以逆转 CUMS 引起的棘密度和突触可塑性相关蛋白 95 (PSD95)。总之，这项研究强调了 WS6 对 CUMS 诱导的抑郁症的神经保护和抗抑郁样作用，并通过海马内神经发生的变化提出了这种保护的可能机制。这些发现揭示了 WS6 在治疗 MDD 神经元退化的临床试验中的治疗保护作用。