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Neuroprotective Effect of Methanolic Ajwa Seed Extract on Lipopolysaccharide-Induced Memory Dysfunction and
Vasudevan Mani1, Minhajul Arfeen2, Devendra Kumar Dhaked3
1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Abstract:
Islamic literature has indicated that daily consumption of Ajwa dates heals a variety of chronic diseases and disorders. The current research investigates the neuroprotective effect of methanolic Ajwa seed extract (MASE) on lipopolysaccharide (LPS)-induced cognitive deficits using multiple approaches. For animal studies, MASE (200 and 400 mg/kg, p.o.) was administrated for thirty consecutive days, and four doses of LPS (250 µg/kg, i.p.) were injected to induce neurotoxicity. Memory functions were evaluated using elevated plus-maze and novel object recognition tests. Acetylcholine (ACh) and neuroinflammatory markers (cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-β1) were estimated in brain tissues. Studies of molecular docking and dynamics were conducted to provide insight into the molecular-level mechanisms. MASE administration resulted in a significant reversal of LPS-induced memory impairment in both maze models. Both doses of MASE elevated the ACh levels in an LPS-treated rat brain. In addition, the extract lowered COX-2 and proinflammatory cytokines (TNF-α and IL-6) while increasing anti-inflammatory cytokines (IL-10 and TGF-β1) in LPS-treated brain tissues. Molecular modeling results revealed that the compound's ellagic acid, epicatechin, catechin, kaempferol, quercetin, and apigenin have the potential to act as a dual inhibitor of acetylcholinesterase (AChE) and COX-2 and can be responsible for the improvement of both cholinergic and inflammatory conditions, while the cinnamic acid, hesperidin, hesperetin, narengin, and rutin compounds are responsible only for the improvement of cholinergic transmission. The above compounds acted by interacting with the key residues Trp84, Asp72, Gly118, Ser200, Tyr334, and His440, which are responsible for the hydrolysis of ACh in AChE, while the COX-2 is inhibited by interacting with the residues (Val349, Leu352, Tyr355, Tyr385, Ala527, Ser530, and Leu531) of the hydrophobic channel. By promoting cholinergic activity and protecting neuroinflammation in the rat brain, MASE provides neuroprotection against LPS-induced cognitive deficits. Our preliminary findings will help with further drug discovery processes related to neuroinflammation-related neurodegeneration.
Insights
Methanolic Ajwa seed extract (MASE) reversed lipopolysaccharide-induced memory deficits in rats by enhancing acetylcholine levels and reducing neuroinflammation. Molecular docking suggests compounds in MASE inhibit acetylcholinesterase and cyclooxygenase-2, offering neuroprotection against cognitive decline.
Area of Science:
- Neuroscience
- Pharmacology
- Computational Chemistry
Background:
- Islamic literature suggests Ajwa dates possess therapeutic properties for chronic diseases.
- Lipopolysaccharide (LPS) is used to induce neurotoxicity and cognitive deficits in animal models.
- Neuroinflammation and cholinergic system dysfunction are implicated in cognitive impairment.
Purpose of the Study:
- To investigate the neuroprotective effects of methanolic Ajwa seed extract (MASE) against LPS-induced cognitive deficits.
- To elucidate the underlying molecular mechanisms of MASE's action.
- To evaluate MASE's impact on memory, acetylcholine levels, and neuroinflammatory markers.
Main Methods:
- Animal study involving MASE administration and LPS injection to induce neurotoxicity.
- Behavioral tests (elevated plus-maze, novel object recognition) to assess memory function.
- Biochemical analysis of brain tissues for acetylcholine and neuroinflammatory markers (COX-2, TNF-α, IL-6, IL-10, TGF-β1).
- Molecular docking and dynamics simulations to explore interactions with target enzymes.
Main Results:
- MASE significantly reversed LPS-induced memory impairment in behavioral tests.
- MASE administration increased acetylcholine levels in the brains of LPS-treated rats.
- MASE reduced levels of cyclooxygenase-2 and pro-inflammatory cytokines (TNF-α, IL-6) while increasing anti-inflammatory cytokines (IL-10, TGF-β1).
- Molecular modeling indicated that compounds in MASE can inhibit acetylcholinesterase (AChE) and cyclooxygenase-2 (COX-2).
Conclusions:
- Methanolic Ajwa seed extract (MASE) demonstrates significant neuroprotective effects against LPS-induced cognitive deficits.
- MASE promotes cholinergic activity and reduces neuroinflammation, contributing to memory improvement.
- The findings support MASE as a potential therapeutic agent for neurodegenerative diseases and warrant further drug discovery efforts.
