Article

Multiple Targets of Polyphenols from Picralima nitida on Blood Glucose Regulatory Enzymes

Emmanuel Eimiomodebheki Odion, Paul Ejime Elede, Kingsley Peter Akpeh, Adaeze Phina Uchendu, Theresa Chioma Umeji

Background and Purpose: Picralima nitida (Apocynaceae) is traditionally used in many African communities to manage diabetes mellitus.  This therapeutic effect may be attributed to the presence of different phytochemicals that act on multiple targets. This study aimed to profile polyphenols in the stem of P. nitida, evaluate its antioxidant potential, and investigate the interactions of the identified polyphenols against selected antidiabetic protein targets through molecular docking.

Methods: High Pressure Liquid Chromatography was used to profile the methanol-dichloromethane extract of P. nitida (MDPN), while antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and Ferric Reducing Antioxidant Power (FRAP) assays. Molecular interaction of the identified polyphenols with ?-glucosidase (AGL) and Dipeptidyl peptidase-4 (DPP-4) was evaluated through an in silico study.

Results: Seven polyphenols were identified, with kaempferol (136.01 ppm) and vanillic acid (134.54 ppm) occurring as the most abundant. A concentration-dependent increase in percentage inhibition was observed in DPPH and FRAP assays. The IC₅₀ values for DPPH and FRAP were 89.37 µg/mL (R²=0.962) and 10.271 µg/mL (R²=0.973), respectively. Polyphenols intermingle with the AGL complex by hydrophobic interactions involving amino acid residues: Trp432, Trp329, Phe601, hydrogen bonds: Asp232, Asp568, His626, Asp357, Arg552, and van der Waals: Trp467, Ile358, Trp565, Phe476, Ser474, Ile396. Also, the DPP-4 complex engaged in hydrophobic interactions with the amino acid residues Phe357, Tyr666, Tyr662, hydrogen bonds with Asn710, and van der Waals interactions with His740, Glu206, Ser209, Tyr631, Val656, Val711, and Trp659. Epigallocatechin and myricetin exhibited the highest binding affinities and inhibitory potentials against AGL, whereas myricetin, quercetin, and kaempferol demonstrated superior binding affinities towards DPP-4. Epigallocatechin, epicatechin, vanillic acid, and gallic acid showed selective preference for DPP-4, while myricetin, quercetin, and kaempferol displayed greater selectivity for AGL.

Conclusion: These findings suggest that MDPN contains polyphenols that exhibit antioxidant activity via hydrogen-atom and electron-donation mechanisms and selectively target AGL and DPP-4.