Embelin, a potent molecule for Alzheimer's disease: Embelin, a potent molecule for Alzheimer's disease A proof of concept from blood-brain barrier permeability, acetylcholinesterase inhibition and molecular docking studies Embelin

Saatheeyavaane Bhuvanendran, Nur Aziah Hanapi, Nafees Ahemad, Iekhsan Othman, Siti Rafidah Yusof, Mohd Farooq Shaikh

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    6 Citations (Scopus)

    Abstract

    Embelin is well-known in ethnomedicine and reported to have central nervous system activities. However, there is no report on blood-brain barrier (BBB) permeability of embelin. Here the BBB permeability of embelin was evaluated using in vitro primary porcine brain endothelial cell (PBEC) model of the BBB. Embelin was also evaluated for acetylcholinesterase (AChE) inhibitory activity and docking prediction for interaction with AChE and amyloid beta (Aβ) binding sites. Embelin was found to be non-toxic to the PBECs and did not disturb the PBEC barrier function. The PBECs showed restrictive tight junctions with average transendothelial electrical resistance of 365.37 ± 113.00 Ω.cm2, for monolayers used for permeability assays. Permeability assays were conducted from apical-to-basolateral direction (blood-to-brain side). Embelin showed apparent permeability (Papp) value of 35.46 ± 20.33 × 10−6 cm/s with 85.53% recovery. In vitro AChE inhibitory assay demonstrated that embelin could inhibit the enzyme. Molecular docking study showed that embelin binds well to active site of AChE with CDOCKER interaction energy of −65.75 kcal/mol which correlates with the in vitro results. Docking of embelin with Aβ peptides also revealed the promising binding with low CDOCKER interaction energy. Thus, findings from this study indicate that embelin could be a suitable molecule to be further developed as therapeutic molecule to treat neurological disorders particularly Alzheimer's disease.

    Original languageEnglish
    Article number495
    Number of pages10
    JournalFrontiers in Neuroscience
    Volume13
    Issue numberMAY
    DOIs
    Publication statusPublished - 16 May 2019

    Keywords

    • Acetylcholinesterase inhibitor
    • Amyloid beta peptides
    • Blood-brain barrier
    • Embelin
    • Molecular docking
    • Permeability

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