Abstract: Alkylresorcinols from wheat bran have inhibitory activities on α-glucosidase, demonstrating the potential to control postprandial hyperglycemia. However, the molecular mechanisms have not been clarified yet. 5-n-Heneicosylresorcinol is the most abundant alkylresorcinol homologue in wheat bran. In this context, fluorescence spectroscopy and circular dichroism (CD) spectroscopy along with molecular docking technique were used to study the molecular mechanisms for the inhibition of 5-n-heneicosylresocinol on α-glucosidase. The results showed the intrinsic fluorescence of α-glucosidase was quenched by 5-n-heneicosylresocinol through a static quenching procedure. The binding constants at 298, 304 and 310 K were 149.8, 46.2 and 20.3 L/mol, respectively. The interaction between 5-n-heneicosylresocinol and α-glucosidase changed the secondary structure of α-glucosidase, as indicated by decreased α-helix content and increased contents of β-sheet, β-turn and random coil. Hydrogen bonds were formed between the 3–OH group on the benzene ring of 5-n-heneicosylresocinol and the –COOH group on Tyr158 in α-glucosidase, between the hydrogen atom of the 5–OH group on the benzene ring and the hydrogen atom of the –NH2 group on Lys156, and between the oxygen atom of the 5–OH group on the benzene ring and the oxygen atom of the –COOH group on Leu313. Hydrophobic interaction between the alkyl chain of 5-n-heneicosylresocinol and hydrophobic amino acid residues in α-glucosidase such as Phe159, Pro312, Phe314 and Asn415 was another important force to maintain the stability of the complex.

Key words: 5-n-heneicosylresocinol, α-glucosidase, inhibition, molecular mechanisms