Abstract:
Type 2 diabetes mellitus(T2DM) is the type of diabetes mellitus, is emerging as a
challenging global epidemic. Although there are various therapies that are available to treat
type 2 diabetes mellitus, they have certain side effects to health, so researchers are trying
to introduce new alternative therapeutic ways that have less health issues. There are various
factors that are involved in the development of T2DM that include genetic predisposition,
sedentary lifestyle, imbalanced diet and obesity. Phytochemical analysis and antioxidant
assays such as DDPH and FRAP were performed to evaluate and compare antioxidant
potential of ethanolic extract of Zingiber officinale along with protein denaturation
inhibition assay to determine its anti-inflammatory activity in comparison to Anasid. Using
Cytoscape with cytoHubba extension, HUB genes were shortlisted, and the top 3 genes
were selected: ESR1, EGFR, and SHIP2. GC-MS analysis of ethanolic extract was
performed to get list of compounds that are present in extract. Various filters such as drug
likeliness, ADME/T, Lipinski rule, BOILED EGG, and SWISS ADME filters were applied
to shortlist the compounds. Out of 236, 7 compounds were shortlisted that was further used
for docking with top ranked genes. The name of compounds wasPregn-4-ene-3,20-dione,
5,11-Dihydro-11-[4-[2-(N-[4-amino-1-oxobutyl] amino)ethyl], 6.beta.-
Hydroxymethandienone 2TMS derivative, 2,4-Bis(hydroxylamino)-5-nitropyrimidine, 5-
Heptenoic acid ethyl ester, 3-.beta.-d-Ribofuranosylpyrazolo[4,3-d]pyrimidin-5,7-4H 6H,
5-Methyl-2-(6-methylhept-5-en-2-yl)phenol, and trans-p-mentha-1(7),8-dien-2-ol. The
structures of genes were downloaded from PDB and further used for docking by using pyrx
software. The best docked compound was 5,11-Dihydro-11-[4-[2-(N-[4-amino-1-
oxobutyl] amino) ethyl] with all these genes. The results of docking were also compared
with the inhibitors that showed less affinity with ESR1. This compound was further
selected for MD simulation. Further testing is required to verify these compounds for their
efficiency as drug candidates against the protein for the treatment of T2DM.
