Identifying the alpha-glucosidase inhibitory potential of dietary phytochemicals against diabetes mellitus type 2 via molecular interactions and dynamics simulation

Abstract

The research aims to identify the inhibitory potential of natural dietary phytochemicals against non-insulinotropic target protein alpha-glucosidase and its possible implications to diabetes mellitus type 2.A data set of sixteen plant-derived dietary molecules viz., 4,5-dimethyl-3-hydroxy-2(5H)-furanone, apigenin, bromelain, caffeic acid, cholecalciferol, dihydrokaempferol 7-o-glucopyranoside, galactomannan, genkwanin, isoimperatorin, luteolin, luteolin 7-o-glucoside, neohesperidin, oleanoic acid, pelargonidin-3-rutinoside, quercetin, and quinic acid were taken to accomplish molecular docking succeeded by their comparison with known inhibitors including acarbose, miglitol, voglibose, emiglitate, and 1-deoxynojirimycin. Among all phyto-compounds, bromelain (ΔG: -9.54 kcal/mol), cholecalciferol (-8.47 kcal/mol), luteolin (-9.02 kcal/mol), and neohesperidin (-8.53 kcal/mol) demonstrated better binding interactions with alpha-glucosidase in comparison to the best-known inhibitor, acarbose (ΔG: -7.93 kcal/mol). Molecular dynamics simulation of 10 ns duration, CYP450 site of metabolism identification, and prediction of activity spectra for substances depicted the bromelain as the most stable inhibitor compared to luteolin and acarbose. Findings of molecular interactions, molecular dynamics study, metabolism, and biological activity prediction proved bromelain as a potential alpha-glucosidase inhibitor. Thus, bromelain might be helpful as an insulin-independent therapeutic molecule towards controlling and managing diabetes mellitus type 2.

Essential Oils of Alpinia vietnamica Rhizomes and Leaves: Chemical Composition, Cytotoxicity, α-Glucosidase Inhibition, and Molecular Docking Approach

“…18,19 We used redocking of (3 R ,5 R ,7 R )-octane-1,3,5,7-tetracarboxylic acid as the enzyme substrate. 20 The setup study was used to assess the reliability of the docking procedure. The result showed an root mean square deviation value of 1.23957 Å (<2 Å), indicating that the docking protocol is suitable for the current study as depicted in Figure 2.…”

Identification of potential diagnostic biomarkers and immune infiltration features in diabetic foot ulcer by bioinformatics analysis and validation

“…Extracellular nucleotide pyrophosphatase/phosphodiesterase family (E-NPPs) is widely involved in many regulatory processes, such as nucleotide cycle, pyrophosphate level regulation, phospholipid signaling regulation, cell movement stimulation, insulin receptor regulation, and activation of some extracellular kinases. Abnormal expression of E-NPPs was found in many diseases, such as bone mineralization disorder, abnormal cell movement and metastasis, angiogenesis, tumor invasion, type 2 diabetes, and others (14)(15)(16). A previous study found that NPP1 had the effect of anti-insulin and inhibited the phosphorylation of insulin receptors stimulated by insulin (17).…”

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

“…Therefore, only these ligands were taken forward for MD studies. [42][43][44][45] Vdw: Van der Waals, HB: Conventional Hydrogen Bond, CHB: Carbon Hydrogen Bond.…”