Inhibition mechanism of alpha-amylase, a diabetes target, by a steroidal pregnane and pregnane glycosides derived from Gongronema latifolium Benth

• DOI: 10.3389/fmolb.2022.866719
• Publication Date: 2022-08-10T06:15:27Z
• Authors: Oludare M. Ogunyemi; Gideon A. Gyebi; Afolabi Saheed; Jesse Paul; Victoria Nwaneri-...; Olufunke Olorundare; Joseph Adebayo; Mamoru Koketsu; Nada Aljarba; Saad Alkahtani; Gaber El-Saber Ba...; Charles O. Olaiya
• Keywords: Pregnane; Pregnane X receptor; Acarbose; Alpha-glucosidase; Alpha-amylase; IC50; Docking (animal)

Alpha-amylase is widely exploited as a drug target for preventing postprandial hyperglycemia in diabetes and other metabolic diseases. Inhibition of this enzyme by plant-derived pregnanes not fully understood. Herein, we used vitro, silico, vivo studies to provide further insights into the alpha-amylase inhibitory potential selected pregnane-rich chromatographic fractions four steroidal pregnane phytochemicals (SPPs), viz: marsectohexol (P1), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin (P2), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (P3), 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-canaropyranosyl]-17β-marsdenin (P4) derived from Gongronema latifolium Benth. The results revealed that SPPs source (P1-P4) exhibited against porcine pancreatic vitro. Compounds P1 P2 with IC50 values 10.01 12.10 µM, respectively, showed greater than reference acarbose (IC50 = 13.47 µM). Molecular docking analysis suggests had strong binding affinity (PPA), human (HPA), salivary (HSA), interacting key active site residues through an array hydrophobic interactions hydrogen bonds. Glu233 Asp300 may disrupt their roles acid-base catalytic mechanism proper orientation polymeric substrates, respectively. amylase were maintained dynamic environment indicated root mean square deviation, radius gyration, surface accessible area, number bonds computed trajectories obtained 100-ns molecular dynamics simulation. Key loop regions HPA contribute substrate flexibility interaction toward compounds fluctuation. Furthermore, significantly reduced blood glucose levels area under curve albino rats which orally challenged starch. Therefore, its constituent be inhibitors oral policy impeding rise.