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

Autor: Ogunyemi OM; Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria.; Nutritional and Industrial Biochemistry Unit, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria., Gyebi GA; Department of Biochemistry, Faculty of Science and Technology Bingham University, Nasarawa, Nigeria.; Natural Products and Structural (Bio-Chem)-informatics Research Laboratory (NpsBC-Rl), Bingham University, Nasarawa, Nigeria., Saheed A; Faculty of Basic Medical Sciences, Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Ilorin, Ilorin, Nigeria., Paul J; Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria., Nwaneri-Chidozie V; Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria., Olorundare O; Faculty of Basic Medical Sciences, Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Ilorin, Ilorin, Nigeria., Adebayo J; Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria., Koketsu M; Faculty of Engineering, Department of Chemistry and Biomolecular Science, Gifu University, Gifu, Japan., Aljarba N; Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia., Alkahtani S; Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt., Olaiya CO; Nutritional and Industrial Biochemistry Unit, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
Jazyk: angličtina
Zdroj: Frontiers in molecular biosciences [Front Mol Biosci] 2022 Aug 10; Vol. 9, pp. 866719. Date of Electronic Publication: 2022 Aug 10 (Print Publication: 2022).
DOI: 10.3389/fmolb.2022.866719
Abstrakt: 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 is not fully understood. Herein, we used in vitro , in silico , and in vivo studies to provide further insights into the alpha-amylase inhibitory potential of selected pregnane-rich chromatographic fractions and 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), and 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 the SPPs source pregnane-rich chromatographic fractions and the SPPs (P1-P4) exhibited inhibitory potential against porcine pancreatic alpha-amylase in vitro . Compounds P1 and P2 with IC 50 values 10.01 and 12.10 µM, respectively, showed greater inhibitory potential than the reference acarbose (IC 50 = 13.47 µM). Molecular docking analysis suggests that the SPPs had a strong binding affinity to porcine pancreatic alpha-amylase (PPA), human pancreatic alpha-amylase (HPA), and human salivary alpha-amylase (HSA), interacting with the key active site residues through an array of hydrophobic interactions and hydrogen bonds. The strong interactions of the SPPs with Glu233 and Asp300 residues may disrupt their roles in the acid-base catalytic mechanism and proper orientation of the polymeric substrates, respectively. The interactions with human pancreatic amylase were maintained in a dynamic environment as indicated by the root mean square deviation, radius of gyration, surface accessible surface area, and number of hydrogen bonds computed from the trajectories obtained from a 100-ns molecular dynamics simulation. Key loop regions of HPA that contribute to substrate binding exhibited flexibility and interaction potential toward the compounds as indicated by the root mean square fluctuation. Furthermore, P1 significantly reduced blood glucose levels and area under the curve in albino rats which were orally challenged with starch. Therefore, Gongronema latifolium and its constituent SPPs may be exploited as inhibitors of pancreatic alpha-amylase as an oral policy for impeding postprandial blood glucose rise.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Ogunyemi, Gyebi, Saheed, Paul, Nwaneri-Chidozie, Olorundare, Adebayo, Koketsu, Aljarba, Alkahtani, Batiha and Olaiya.)
Databáze: MEDLINE
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