👤 Mohammed F El-Yamany

Major depressive disorder (MDD) is a complex neuropsychiatric disorder with multifactorial origins involving oxidative stress, neuroinflammation, neurotransmitter imbalance, and HPA axis dysfunction. Conventional treatments are often limited by side effects and suboptimal efficacy, confirming the need for alternative therapies. This study investigates the antidepressant-like and neuroprotective potential of selenium nanoparticles biosynthesized using epigallocatechin gallate (SeNPs-EGCG) in a rat model of depression induced by chronic mild stress. Six groups of seven rats each were used in a model of depression caused by chronic unpredictable mild stress (CUMS): control, depressed, depressed treated with escitalopram, epigallocatechin gallate (EGCG), sodium selenite (Na Behavioral assays demonstrated that SeNPs-EGCG significantly reversed depression-like behaviors, evidenced by increased sucrose preference and grooming frequency in the SeNPs-EGCG-treated group compared to the depressed group. Biochemically, SeNPs-EGCG restored antioxidant defense by increasing GSH, SOD, and CAT levels, while reducing lipid peroxidation to near-normal levels. Neuroinflammatory markers such as TNF-α, IL-1β, IL-8, and NF-κB were markedly downregulated in the SeNPs-EGCG group. Molecular results also showed a slowing down of proapoptotic signals (Bax and Caspase-3) and upregulation of anti-apoptotic Bcl-2 and neurotrophic factor BDNF. Importantly, SeNPs-EGCG modulated key monoamines, increasing serotonin and DA levels. Compared to both EGCG and sodium selenite controls, SeNPs-EGCG demonstrated superior efficacy, comparable to the standard antidepressant escitalopram. The results underscore the multi-targeted mechanism of SeNPs-EGCG and suggest its promising role as a novel nano-based therapeutic strategy for depression. Show less

Sporadic Alzheimer's disease (SAD) represents a major health concern especially among elderly. Noteworthy, neuroinflammation and oxidative stress are highly implicated in AD pathogenesis resulting in enhanced disease progression. Moreover, most of the available anti-Alzheimer drugs have several adverse effects with variable efficacy, therefore new strategies, including agents with anti-inflammatory and antioxidant effects, are encouraged. Along these lines, canagliflozin (CAN), with its anti-inflammatory and anti-apoptotic activities, presents a promising candidate for AD treatment. Therefore, this study aimed to evaluate the therapeutic potential of CAN via regulation of AMPK/SIRT-1/BDNF/GSK-3β signaling pathway in SAD. SAD model was induced by intracerebroventricular streptozotocin injection (ICV-STZ;3 mg/kg, once), while CAN was administered (10 mg/kg/day, orally) to STZ-treated mice for 21 days. Behavioral tests, novel object recognition (NOR), Y-Maze, and Morris Water Maze (MWM) tests, histopathological examination, total adenosine monophosphate-activated protein kinase (T-AMPK) expression, p-AMPK, and silent information regulator-1 (SIRT-1) were evaluated. Furthermore, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3β (GSK-3β), acetylcholinesterase (AChE), Tau protein, insulin-degrading enzyme (IDE), nuclear factor erythroid-2 (Nrf-2), interleukin-6 (IL-6), nuclear factor kappa-B-p65 (NFκB-p65), beta-site APP cleaving enzyme 1 (BACE-1), and amyloid beta (Aβ) plaque were assessed. CAN restored STZ-induced cognitive deficits, confirmed by improved behavioral tests and histopathological examination. Besides, CAN halted STZ-induced neurotoxicity through activation of p-AMPK/SIRT-1/BDNF pathway, subsequently reduction of GSK-3β, Tau protein, AChE, NFκB-p65, IL-6, BACE-1, and Aβ plaque associated with increased IDE and Nrf-2. Consequentially, our findings assumed that CAN, via targeting p-AMPK/SIRT-1 pathway, combated neuroinflammation and oxidative stress in STZ-induced AD. Thus, this study highlighted the promising effect of CAN for treating AD. Show less