Screening and druggability analysis of Zingiber officinale bioactive compounds against diabetes mellitus using a computational approach

Abstract

The prevalence of diabetes mellitus is increasing globally at an alarming rate. It is a metabolic disorder characterized by elevated blood glucose levels due to either inadequate insulin production or ineffective use of insulin, which eventually leads to micro and macrovascular complications. The present study is aimed to screen antidiabetic compounds of ginger using an in silico approach. Total 132 ginger phytocompounds are screened based on Druglikeness properties using DruLito software. The key targets such as GCK, PPAR-γ, and DPP4 are selected from 18 diabetes targets using Network analysis. The molecular docking is performed between the selected key targets and bioactive compounds of ginger using PyRx. A total of four bioactives such as compound-I (curcumin), compound-II (7-(3′,4′-Dihydroxy-5′-methoxyphenyl)-5-hydroxy-1-(4″-hydroxy-3″-methoxyphenyl)heptan-3-one), compound-III (1,7-bis(3′,4′-Dihydroxyphenyl)-3,5-diacetate heptane), compound-IV (1,7-bis(4′- Hydroxy -3′-methoxyphenyl)-3,5-diacetate heptane) are selected based on their docking score. Among these bioactives, compound I showed the highest binding affinity with GCK, DPP4, and PPAR-γ, with scores of -8.0, -7.8, and -7.5 kcal/mol, respectively, followed by compound II -7.4, -7.6 and -7.8 kcal/mol, compound III -7.2,-7.4, and -7.5 kcal/mol, and compound IV -7.1,-7.1,and -7.7 kcal/mol respectively, though slightly lower than compound I. All four compounds (Compound-I, II, III, IV) are found to exhibit high absorption rates (60-80%), within the acceptable range for Caco-2 permeability and skin permeability. However, they show poor distribution across the blood-brain barrier and acted as substrates for CYP3A4 in drug metabolism. Therefore, our findings suggest that these four bioactive compounds could be potential drug candidates for managing diabetes by regulating insulin synthesis, glucose, and lipid metabolism.