Morin hydrate attenuates chronic stress-induced memory impairment and degeneration of hippocampal subfields in mice: The role of oxidative, nitrergic and neuroinflammatory pathways.

Abstract

Morin hydrate (MH) is the major flavonoid constituent of Morus alba acclaimed to have antioxidant, anti-inflammatory, anti-stress and neuroprotective properties. However, report on the effect of MH on memory performance and the underlying mechanism following chronic stress exposure is lacking. The current study aimed at investigating the neuroprotective effect of MH on chronic unpredictable stress (CUS)-induced memory impairment in mice using the Y maze test. Mice were subjected to unpredicted stress for 14 days, during which MH (5, 10 and 20 mg/kg i.p) or 25 mg/kg Ginseng was administered to them. On the 14th day, 1 h after treatment, learning and memory deficit was evaluated using the Y maze test and thereafter brains were harvested for the estimation of glutathione (GSH), lipid peroxidation product; malondialdehyde (MDA) and nitrite. Levels of inflammatory mediators tumor necrosis factor-alpha (TNF-α) and interleukin1-beta (IL-1β), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-кB) expressions were also determined. The hippocampus was stained with hematoxylin-eosin (H&E) to examine any morphological changes in the neurons. Mice exposed to CUS showed evidence of impaired memory and increase levels of MDA, nitrite, TNF-α and IL-1β. Furthermore, CUS reduced GSH level, increased the expressions of iNOS and NFкB immune-positive cells and produced loss of neuronal cells in the hippocampus. The MH treatment however improved memory, reduced MDA and nitrite levels, and enhanced brain GSH levels in CUS-mice. Besides, MH reduced brain levels of TNF-α and IL-1β levels, down regulated the expressions of iNOS and NF-кB and rescue neurons in the hippocampal CA3 region of mice exposed to CUS. The results of the study indicate that MH improved CUS-induced memory impairment, which may be related to its ability to boost antioxidant defense system and suppress neuroinflammatory pathways.