Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies

Mani, Vasudevan; Arfeen, Minhajul; Mohammed, Hamdoon A.; Elsisi, Hossam A.; Sajid, Sultan; Almogbel, Yasser; Aldubayan, Maha; Dhanasekaran, Muralikrishnan; Alhowail, Ahmad

doi:10.1016/j.jsps.2022.03.016

Cited by 17 publications

(13 citation statements)

References 61 publications

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“…The quantitative assessments of the total phenolic contents in the MASE, including the polyphenols, flavonoids, and tannins, showed that these categories of secondary metabolites were present in significant amounts ( Table 1 ). The measurements revealed the presence of a high quantity of the total phenolics measured at 76.06 mg GAE compared to the reported polyphenols in the data extract [ 20 ]. The findings also revealed the presence of a considerable amount of flavonoids and tannin contents, which were measured at the levels of 8.66 QE and 11.48 CE per gram of the extract, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the above-mentioned compounds are considered for molecular docking studies. Our previous studies using an aqueous extract of Sukkri dates and a target fishing approach together indicated acetylcholinesterase (AChE) and COX as potential targets for our observed results [ 20 ]. Therefore, molecular docking was performed for the above-mentioned compounds using AChE (PDB code: 1DX6) and COX-2 (PDB code: 5IKR).…”

Section: Resultsmentioning

confidence: 99%

“…The MASE total tannins content was measured by the method described in the literature by Mani et al (2022) [ 20 ]. A mixture of 1.5 mL of the vanillin solution (4% in methanol) and 750 µL of the concentrated HCl was added to Ajwa extract (200 µL of the 0.1 mg/mL) in a test tube.…”

Section: Methodsmentioning

confidence: 99%

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

Mani

Arfeen

Dhaked

et al. 2023

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Mani

Arfeen

Dhaked

et al. 2023

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“…Our molecular docking studies also displayed a hydrogen bond interaction between the amino group of LEVE and the side chain hydroxyl group of Ser involved in the catalytic triad. LEVE also displayed a hydrogen bond interaction with Gly118, Gly 119, and Gly116, Gly117 in AChE and BuChE, respectively [ 33 ]. The Gly residues of the oxyanion hole stabilize the ACh-AChE reactant complex during the catalysis through two respective hydrogen bonds.…”

Section: Discussionmentioning

confidence: 99%

“…The rats were divided into four groups and each group was limited to seven animals (n = 7). The sample size was decided based on our previously published reports and the methods reported by Arifin and Zahiruddin (2017) [ 33 , 34 , 35 ]. The animal experiments followed the guidelines of the College Pharmacy Research Center (Ethical Approval ID 2020-CP-14) and the Deanship of Scientific Research of Qassim University under grant number 10223-pharmacy-2020-1-3-I.…”

Section: Methodsmentioning

confidence: 99%

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

et al. 2022

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Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The ‘nootropic-like’ activity could be related to diminished AChE and neuroinflammatory mediator levels.

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Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment

et al. 2023

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Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies

Cited by 17 publications

References 61 publications

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

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

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study

Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment

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