Neuroprotective Effect of Methanolic Ajwa Seed Extract on Lipopolysaccharide-Induced Memory Dysfunction and Neuroinflammation: In Vivo, Molecular Docking and Dynamics Studies

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.

Phoenix dactylifera (Ajwa Dates) Alleviate LPS-Induced Sickness Behaviour in Rats by Attenuating Proinflammatory Cytokines and Oxidative Stress in the Brain

“…These results support the protective effect of PDF against LPS-induced behavioural changes in animals. These results are in agreement with the recent study on the neuroprotective activities of Ajwa seed extract in toxin-induced neuronal insults in animals [27].…”

“…It was evident by its attenuation of behavioural changes, restoration of antioxidant levels, reduction of oxidative and nitrative stress, reduction of proinflammatory cytokines, restoration of water and food intake and attenuation of ALT and AST in LPS-treated animals. These findings are in agreement with research data published on Ajwa dates as neuroprotective and beneficial in memory improvement in neuro-compromised animals [ 27 , 31 ].…”

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis

“…Generally, the animals dislike staying in open and elevated places and prefer to stay in closed and dark areas. Furthermore, shorter TL values support the improvement of their spatial memory [25]. The results of this present study revealed that the extension of TL values on days 1 and 2 was recorded after four doses of DOX in the EPM test, which indicates impairment of learning and memory in rats.…”

Assessing the Influence of Intermittent Alcohol Access on Acrylamide-Induced Neuronal Toxicity in an Experimental Rat Model

“…Firstly, the EPM test was conducted over a period of two days, beginning on day 26 of the treatment timeline, with the subsequent day designated as the retention phase. The EPM test is a widely used neutral behavioral model to study the ability of animals to learn and remember [ 38 , 42 ]. Normally, animals tend to avoid open and elevated areas while exhibiting a preference for closed and dark areas.…”

“…Normally, animals tend to avoid open and elevated areas while exhibiting a preference for closed and dark areas. Additionally, shorter TL values indicate improved spatial memory [ 42 ]. The study findings revealed that on the first day of the EPM test, the ACR + IAE co-administration group exhibited significantly longer TL values and a decline in spatial memory in relation to the control group.…”