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

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-1ß), 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-1ß. 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-1ß 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.

Methyl jasmonate attenuates memory dysfunction and decreases brain levels of biomarkers of neuroinflammation induced by lipopolysaccharide in mice.

Neuroinflammation plays a central role in the etiology and progression of Alzheimer's disease (AD), a neurodegenerative disorder, characterized by a gradual loss of memory functions. Thus, it has been proposed that agents that could reduce inflammatory processes in AD brains might be useful for the treatment of the disease. Methyl jasmonate (MJ) is a bioactive compound, which has been reported to exhibit anti-amnesic and in vitro anti-inflammatory activities. In this study, we further examine its effects on the brain levels of biomarkers of neuroinflammation in lipopolysaccharide (LPS)-induced memory deficits in mice. Mice (n=6) were pretreated intraperitoneally with MJ (10-40mg/kg), donepezil (DP) (1mg/kg) or vehicle (10mL/kg) for 30min prior to injection of LPS (250µg/kg, i.p) daily for 7days. Thirty minutes after LPS administration on day 7, memory function was assessed using Y-maze test. After Y-maze test, the levels of biomarkers of neuroinflammation: prostaglandin E2 (PGE2), tumor necrosis factor α (TNFα) and interleukin 1ß (IL1ß) were estimated in brain tissue homogenates using ELISA. Expressions of positive cells of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB) and amyloid-beta (Aß) in the prefrontal cortex were also assessed using immunohistochemistry technique. Our data showed that MJ (10, 20 and 40mg/kg) significantly (p<0.05) reversed LPS-induced memory deficits in mice. The increased brain levels of PGE2, TNFα and IL1ß in LPS-treated mice were significantly (p<0.05) reduced by MJ indicating anti-neuroinflammatory activity. MJ also suppressed the expression of COX2, iNOS and NFκB, which further suggest anti-neuroinflammation. The increased brain level of Aß in LPS-treated mice was significantly (p<0.05) suppressed by MJ suggesting anti-amyloidogenesis-like effect. Our present data showed that MJ attenuated LPS-induced memory dysfunction via mechanisms involving inhibition of pro-inflammatory mediators and beta-amyloid generation in mice.