Open AccessDetermination of Potential Anti-Alzheimer Activity of Gentiopicroside and Isoorientin Using Molecular Docking Studies
Author(s) -
Nida Nur DERELI-CALISKAN,
Mehmet Tahir Hüsunet,
Hasan Basri İla,
Işık Didem Karagöz
Publication year - 2021
Publication title -
the eurasia proceedings of science, technology, engineering and mathematics
Language(s) - English
Resource type - Journals
ISSN - 2602-3199
DOI - 10.55549/epstem.1038383
Subject(s) - autodock , epigenetics , isoorientin , histone , docking (animal) , histone deacetylase , neuroprotection , pharmacology , chemistry , biology , biochemistry , medicine , antioxidant , in silico , dna , gene , nursing , flavonoid
Alzheimer's disease (AD) is the most common type of dementia worldwide, involving a multifactorial combination of environmental, genetic and epigenetic factors. It is characterized by the accumulation of abnormal amyloid beta (Aß) and tau fibrillar tangles, oxidative stress, neuroinflammation, and disruption of autophagy mechanisms. The agents used for the treatment of the disease only prevent the symptoms of the disease. Epigenetic modifications such as DNA methylations and histone modifications that occur in learning and memory processes have come to the fore in the search for new and reliable potential therapeutic agents for AD. Against these multiple mechanisms of AD, natural products are currently considered an alternative strategy for the discovery of new multipotent drugs. Phytocompounds of Gentiana olivieri, Gentiopicroside and Isoorientin, which have been known to have many benefits for health, act as a neuroprotective effect by acting as an anti-inflammatory and antioxidant. Based on this, in order to determine the possible effects of Gentiopicroside and Isoorientin phytocompounds on Sirtüin-1 (SIRT1), Sirtüin-2 (SIRT2), Sestrin 2 (SESN2), Histone deacetyl transferase-6 (HDAC6) and divalent metal transporter 1 (DMT1) enzymes, which are seen as targets in AD, molecular docking analysis was carried out. AutoDock 4.0 software was used to predict the interaction of ligands with possible active binding sites on the target molecule crystal structure. As a result of the analyzes, the best coupling occurred between the Gentiopicroside and DMT1 and HDAC6 enzymes. In the light of this information, it can be suggested that the molecular clamping analysis is carried out by the neuroprotective effect of Gentiopicroside by DMT1 enzyme inhibition, while Izoorientine performs through the HDAC6 enzyme. As a result, it is thought that our results will contribute to the search for new therapeutic agent studies using epigenetic approaches against AD.