Computational Screening for Novel α-glucosidase Inhibitory Peptides from Chlamys nobilis Adductor Muscle as a Potential Antidiabetic Agent

Haisheng Lin ¹ Wen Wang ¹ Lei Du ^2* Jialong Gao ¹ Wenhong Cao ¹ Huina Zheng ¹ Zhongqin Chen ¹ Xiaoming Qin ¹ Yuanwei Liang ^3*

• ¹ College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China
• ² State Key Laboratory of Bioreactor Engineering, Department of Food Science and Engineering, East China University of Science and Technology, Shanghai, China
• ³ College of Chemistry and Environment, Guangdong Ocean University, Zhanjiang, China

This study aimed to evaluate the adjuvant hypoglycemic function of enzyme hydrolyzate (EHCA) from Chlamys nobilis in mice and to identify α-glucosidase inhibitory peptides. α-glucosidase inhibitory and radical scavenging ability of EHCA were determined in vitro, and the effects on blood glucose regulation and the antioxidant activity in vivo were evaluated. Results show that EHCA had good α-glucosidase inhibitory activity and radical scavenging activity for 2,2-diphenyl-1-picrylhydrazyl (DPPH). EHCA significantly improved the glucose tolerance of mice, reduced malondialdehyde and increased the superoxide dismutase activity in liver. Five novel peptides were picked out by LC-MS/MS and then confirmed in silico that Lys-Leu-Asn-Ser-Thr-Thr-Glu-Lys-Leu-Glu-Glu and Thr-Asp-Ala-Asp-His-Lys-Phe have strong inhibitory effect on α-glucosidase (IC50 value of 144.89 μM and 136.96 μM, respectively). Hydrogen bonds, van der Waals forces and hydrophobic interactions were the main drivers of the interaction of peptides with α-glucosidase. These findings could pave the way for the development of alternative α-glucosidase inhibitors.