基于分子对接和网络药理学方法研究桑叶中的新型α-葡萄糖苷酶抑制肽OA

Mulberry leaves are a rich source of high-quality protein and possess the potential to yield bioactive peptides.This study identified novel α-glucosidase inhibitory peptides from mulberry leaf proteolytic products based on peptidomics identification and the structure-activity relationships of active peptides.Through molecular docking and network pharma-cology predictions,the anti-diabetic mechanisms of these novel α-glucosidase inhibitory peptides were elucidated.The re-sults indicated that two novel α-glucosidase inhibitory peptides were identified:ANSTGSRL(IC50=0.314 mg/mL)and LAKLLHSK(IC50=0.183 mg/mL).LAKLLHSK exhibited a higher content of β-sheet structure and a lower content of α-helix and random coil structures compared to ANSTGSRL.The gastrointestinal digestion process enhanced the release of α-glucosidase inhibitory activity for both peptides,achieving over 85%enzyme inhibition.Molecular docking analysis re-vealed that the two peptides tightly bound to the active residue sites of α-glucosidase(Val335,Val334,Pro230 and Gly228),primarily through multiple hydrogen bonds and hydrophobic interactions,thereby exerting their α-glucosidase inhibitory ac-tivity.Network pharmacology predictions indicated that two peptides,ANSTGSRL and LAKLLHSK,could interact with over ten key targets,including MAPK1,CASP3,STAT1,ERBB2 and AKT3.KEGG pathway enrichment analysis re-vealed that the anti-diabetic pathway associated with these peptides involves multiple complex signaling pathways,includ-ing the TNF,cAMP,PI3K-Akt,and MAPK pathways,as well as insulin resistance.In conclusion,the novel mulberry leaf peptides ANSTGSRL and LAKLLHSK exhibited strong α-glucosidase inhibitory activity and potential glucose regulation effects.This study could provide a theoretical reference for the high-value utilization of mulberry leaf protein resources.