Major depressive disorder (MDD) is a prevalent psychiatric disorder with a complex pathogenesis influenced by various factors. Recent research has highlighted a significant connection between psychological stress and MDD, with inflammation playing a central role in this relationship. Studies have demonstrated that peripheral immune changes in patients with MDD and in mouse models of social stress are closely linked to depressive symptoms. These findings suggest that targeting peripheral immune factors could represent a novel approach for treating stress-related neuropsychiatric disorders. Stress triggers a cascade of inflammatory responses, leading to disruptions in neurotransmitter metabolism and reduced synaptic plasticity. These changes exacerbate depression and contribute to cognitive decline. This study examines the bidirectional relationship between MDD and stress, focusing on the role of inflammation in this complex interplay. Recent studies have identified specific immune factors that are elevated in the serum of patients with MDD and stress-exposed mice, indicating a mechanism by which peripheral immune responses can affect central nervous system function and behavior. Furthermore, proteins, such as nuclear factor kappa-B (NF-κB), reportedly play a critical role in the regulation of stress hormones and are associated with depressive behaviors. Understanding these mechanisms is essential for advancing diagnostic, intervention, and treatment strategies for MDD.

Alzheimer’s disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation may improve AD symptoms. This study investigated the neuroprotective effects of Acanthopanax senticosus saponins (ASS) in an AD model induced by streptozotocin (STZ). Here, we characterised a rat model of STZ-induced AD with the parallel deterioration of memory loss and neuroinflammation. Following the end of the treatment with ASS (50 mg/kg for 14 consecutive days), behavioural tests (Morris water maze test, Y-maze test) were performed on the rat, and the molecular parameters (DAPK1, Tau5, p-Tau, NF-κB, IL-1β, TNF-α, and NLRP3) of the rat hippocampus were also assessed. We demonstrated that ASS, which has potent anti-inflammatory effects, can reduce neuroinflammation and prevent cognitive impairment. In the water maze test, ASS-treated groups exhibited significantly increased average escape latency (p < 0.05), the percentage of stay in the target quadrant (p < 0.05), and the number of times each group of rats crossed the platform (p < 0.05) compared to the negative control. And ASS could reduce the phosphorylation of the Tau protein (p < 0.001) and death-associated protein kinase 1 (DAPK1, p < 0.001) in the hippocampal tissue, improving cognitive impairment in STZ-treated rats by suppressing the inflammatory response; the molecular analysis showed a significant reduction in pro-inflammatory markers like NLRP3, IL-1β, TNF-α, and NF-κB (p < 0.001). It was also discovered that the NF-κB inhibitor SN50 had the same effect. Therefore, the present study used ASS through its anti-inflammatory effects to prevent and treat AD. This study highlights the potential efficacy of ASS in alleviating cognitive dysfunction in AD.