Neuroprotective effects of aegeline against LPS-induced memory dysfunction: involvement of hippocampal...

This study aimed to evaluate the neuroprotective effects of aegeline on lipopolysaccharide (LPS) -induced cognitive dysfunction in rats.

The global rise in neuroinflammatory and cognitive disorders demands safe and effective plant-based neuroprotective agents. LPS is a potent endotoxin that triggers inflammation and tissue damage. Aegeline, a hydroxyamide derived from Aegle marmelos, exhibits anti-inflammatory and antioxidant properties. However, its ability to modulate hippocampal cholinergic and proinflammatory cytokine receptors, as well as to protect against LPS-induced memory impairment, remains unexplored.

Aegeline was administered at doses of 5 and 10 mg/kg for seven days to Wistar rats. Behavioral tests included the Y-maze and the Morris water maze (MWM). Biochemical analyses measured acetylcholinesterase (AChE), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), and inflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. Furthermore, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and caspase-3 markers were evaluated. Additionally, in silico molecular docking and molecular dynamics simulations (MDS) were conducted.

Aegeline treatment improved performance in the Y-maze and MWM tests. It reduced AChE, proinflammatory cytokine, NF-κB, oxidative stress marker, and caspase-3 levels. Antioxidant enzymes and ChAT levels were increased. In silico, aegeline showed strong binding to protein 7JRA with a binding energy of -9.289 kcal/mol, respectively. MDS confirmed the stable interactions with key therapeutic targets.

Aegeline improved cognition, reduced inflammation and oxidative stress, and enhanced antioxidant and cholinergic activity. Its strong molecular binding supports its potential as a neuroprotective agent against memory impairment.