Alleviates Chronic Unpredictable Mild Stress (CUMS)-Induced Depressive Cognitive Dysfunction by Regulating the HPA Axis and TLR4/NF-κB Pathway.

Abstract

The purpose of this study was to assess the effects of a 60% ethanolic extract of(EAY) on chronic unpredictable mild stress (CUMS)-induced depressive cognitive dysfunction. The results showed that EAY mitigated CUMS-induced depressive-like behaviors, as confirmed by the sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST). In addition, EAY showed protective effects on cognitive function in the Y-maze and the Morris water maze (MWM) tests. In this regard, EAY alleviated hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis through regulation of corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cytochrome P450 family 11 subfamily B member 1 (CYP11B1), thereby improving the levels of serum cortisol. It suppressed neuroinflammation, oxidative stress, and mitochondrial dysfunction by inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor κ-light-chain-enhancer of the activated B cells (NF-κB) pathway. As a result, cognitive dysfunction was ameliorated through modulation of the cholinergic system, including acetylcholinesterase (AChE), acetylcholine (ACh), and choline acetyltransferase (ChAT), and synaptic plasticity-related factors such as postsynaptic density protein 95 (PSD-95) and growth-associated protein 43 (GAP-43). Based on these results, EAY could potentially be used as a natural therapeutic for prevention of major depressive cognitive impairment.