Abstract
Diabetes mellitus is a chronic metabolic disorder that affects glucose, lipid, and protein metabolism. Targeting these metabolic derangements can optimize the therapeutic strategies for this disease. Utilizing in vitro and in silico models, this study investigated the ability of aqueous and ethanol extracts of Irvingia gabonensis to inhibit α-amylase, α-glucosidase, pancreatic lipase, and protein glycation. High-performance liquid chromatography (HPLC) was used to identify the compounds found in the stem bark of I. gabonensis. In silico analysis determined the binding mode and mechanism of interactions between the enzymes and phytochemicals. With an IC50 value of 11.47 µg/ml, the aqueous extract demonstrated higher inhibitory efficacy against α-amylase compared to the ethanol extract (IC50 19.88 µg/ml). However, the ethanol extract had stronger inhibitory activities against α-glucosidase, pancreatic lipase, and protein glycation compared to the aqueous extract (IC50 values of 3.05, 32.85, 0.0014 versus 25.72, 332.42, 0.018 µg/ml respectively). Quercetin ranked highest in binding energy with α-amylase (-6.6 kcal/mol), α-glucosidase (-6.6 kcal/mol), and pancreatic lipase (-5.6 kcal/mol). This was followed by rhamnetin (6.5, 6.5, and 6.1 kcal/mol respectively). Hydrogen bonding, hydrophobic interactions, and pi-pi stacking are forces responsible for the binding of quercetin and rhamnetin to these enzymes. Molecular dynamics simulation showed that the lead phytochemicals formed stable and energetically stabilized complexes with the target proteins. This study showed that the extracts of I. gabonensis stem bark had significant in vitro anti-diabetic, anti-pancreatic lipase, and anti-protein glycation activities. The strong binding affinities of some of the identified compounds could be responsible for the inhibitory potential of the extracts. I. gabonensis stem bark could be further explored as a natural remedy for the treatment of diabetes mellitus and its complications.
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The study was funded by the National Research Fund (NRF) of the Nigeria Tertiary Education Trust Fund (TETFund) awarded to AO with reference code TETFund/DR&D/CE/NRF/STI/28/VOL1.
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A.O. – funding, conception, experimentation (supervised all experiments), data analysis, manuscript writing, and manuscript revision. C.O. – experimentation (in vitro analysis), data analysis, manuscript writing, and manuscript revision. B.A. – experimentation (in vitro analysis), data analysis, and manuscript revision. O.E. – experimentation (in silico analysis), data analysis, and manuscript revision. E.O. - funding, conception, experimentation (supervised in vitro experiments), data analysis, and manuscript revision. I.O. - funding, conception, reviewed the experimental protocol, and manuscript revision. F.O. - funding, conception, reviewed the experimental protocol, and manuscript revision.
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Omonkhua, A.A., Otitolaiye, C., Aguebor-Ogie, B. et al. Anti-diabetic, anti-pancreatic lipase, and anti-protein glycation potential of Irvingia gabonensis stem bark extracts: in vitro and in silico studies. In Silico Pharmacol. 12, 43 (2024). https://doi.org/10.1007/s40203-024-00219-y
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DOI: https://doi.org/10.1007/s40203-024-00219-y