Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia.
Department of Biology, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia.
Biomolecules. 2023 Sep 30;13(10):1474. doi: 10.3390/biom13101474.
We evaluated the therapeutic potentials of Khudari fruit pulp, a functional food and cultivar of , against neurological disorders. Our results demonstrate a good amount of phytochemicals (total phenolic content: 17.77 ± 8.21 µg GA/mg extract) with a high antioxidant potential of aqueous extract (DPPH assay IC = 235.84 ± 11.65 µg/mL) and FRAP value: 331.81 ± 4.56 µmol. Furthermore, the aqueous extract showed the marked inhibition of cell-free acetylcholinesterase () with an IC value of 48.25 ± 2.04 µg/mL, and an enzyme inhibition kinetics study revealed that it exhibits mixed inhibition. Thereafter, we listed the 18 best-matched phytochemical compounds present in aqueous extract through LC/MS analysis. The computational study revealed that five out of eighteen predicted compounds can cross the BBB and exert considerable aqueous solubility. where 2-{5-[(1E)-3-methylbuta-1,3-dien-1-yl]-1H-indol-3-yl}ethanol (MDIE) indicates an acceptable LD. value. A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with ΔG range between -6.91 and -9.49 kcal/mol, where MDIE has ∆G: -8.67 kcal/mol, which was better than that of tacrine, ∆G: -8.25 kcal/mol. Molecular dynamics analyses of 100 ns supported the stability of the protein-ligand complexes analyzed through RMSD, RMSF, Rg, and SASA parameters. TRP_84 and GLY_442 are the most critical hydrophobic contacts for the complex, although GLU_199 is important for H-bonds. Prime/MM-GBSA showed that the protein-ligand complex formed a stable confirmation. These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.
我们评估了 Khudari 果浆的治疗潜力，Khudari 果浆是一种功能性食品和栽培品种，对神经紊乱有一定疗效。我们的研究结果表明，Khudari 果浆含有大量的植物化学物质（总酚含量：17.77 ± 8.21 µgGA/mg 提取物），具有较高的抗氧化能力，其水提物的 DPPH 测定 IC = 235.84 ± 11.65 µg/mL，FRAP 值为 331.81 ± 4.56 µmol。此外，水提物对无细胞乙酰胆碱酯酶（AChE）的抑制作用显著，IC 值为 48.25 ± 2.04 µg/mL，酶抑制动力学研究表明，它呈现混合抑制。随后，我们通过 LC/MS 分析列出了水提物中 18 种最佳匹配的植物化学物质。计算研究表明，十八种预测化合物中有五种可以穿过血脑屏障并具有相当的水溶性。其中 2-{5-[(1E)-3-甲基丁-1,3-二烯-1-基]-1H-吲哚-3-基}乙醇（MDIE）的 LD 值可接受。分子对接研究表明，这些化合物占据了乙酰胆碱酯酶的关键残基，其 ΔG 值在-6.91 到-9.49 kcal/mol 之间，其中 MDIE 的 ΔG 值为-8.67 kcal/mol，优于他克林的-8.25 kcal/mol。100 ns 的分子动力学分析通过 RMSD、RMSF、Rg 和 SASA 参数支持分析的蛋白-配体复合物的稳定性。TRP_84 和 GLY_442 是复合物中最关键的疏水接触，尽管 GLU_199 对氢键很重要。Prime/MM-GBSA 表明蛋白-配体复合物形成了稳定的构象。这些发现表明，Khudari 果浆的水提物具有显著的抗氧化和乙酰胆碱酯酶抑制潜力，其化合物 MDIE 与靶蛋白形成稳定的构象，尽管 Khudari 日期的这种水果可以成为治疗阿尔茨海默病的更好的功能性食品。需要进一步的研究来通过体内研究充分了解这种植物化合物的治疗作用。
