Dipeptidyl Peptidase-IV Inhibitory Activity and Related Molecular Mechanism of Bovine α-Lactalbumin-Derived Peptides

Abstract

Identifying DPP-IV inhibitory peptides from dietary protein has attracted increased attention. In the present study, bovine α-lactalbumin hydrolysates were generated by alcalase for various hydrolysis times, and DPP-IV inhibitory activity of these hydrolysates was determined. The 4 h hydrolysates displayed the most potent DPP-IV inhibitory activity, with DPP-IV inhibition rate of 82.30 ± 1.39% at concentration of 1.0 mg/mL. DPP-IV inhibitory peptides were isolated from the 4 h-hydrolysates with gel filtration chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC). Using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS), two DPP-IV inhibitory peptides were identified, and their amino acid sequences were Glu-Leu-Lys-Asp-Leu-Lys-Gly-Tyr (ELKDLKGY) and Ile-Leu-Asp-Lys-Val-Gly-Ile-Asn-Tyr (ILDKVGINY), respectively. Furthermore, molecular docking analysis showed that peptides ELKDLKGY and ILDKVGINY could form hydrogen bonds, pi-cation interactions, and salt bridges with DPP-IV. These findings indicated that bovine α-lactalbumin may be a potential source of natural DPP-IV inhibitor.

Characteristics of Food Protein-Derived Antidiabetic Bioactive Peptides: A Literature Update

“…The dietary proteins with highly diverse sequences used as precursors to generate protein hydrolysates and peptides with DPP-IV inhibitory activities have drastically increased over the years. To date, various food commodities such as milk [4,8,35,49,79], fish [36,54], egg [1], or special ones such as quinoa [53], rapeseed [80], and tropical banded cricket [9] are well-known as DPP-IV inhibitor sources. The IC 50 values of various DPP-IV inhibitory hydrolysates collected from the data of scientific reports in the last five years (2016-2020) are summarized in Figure 4 (see original data in Table A2).…”

“…The IC 50 values of various DPP-IV inhibitory hydrolysates collected from the data of scientific reports in the last five years (2016-2020) are summarized in Figure 4 (see original data in Table A2). Nowadays, milk protein hydrolysates released from camel, bovine, and mare are generally considered as potential DPP-IV inhibitory sources [4,8,79]. However, other sources such as marine organisms (Boarfish) [36], plant (Brewers' spent grain and rapeseed) [52,80], and soft-shelled turtle eggs [2] have also attracted consideration as promising DPP-IV inhibitory peptides because of their high proline residue content, an amino acid proven to play a role in the enhancement of DPP-IV inhibition activity.…”

“…Therefore, the general mechanism for in vitro assay of DPP-IV inhibition activity of peptides derived from food hydrolysate could also be exposed using the DPP-IV enzyme of porcine. So far, numerous peptides derived from food hydrolysates were deeply investigated at a molecular level using various available docking software [4,30,38,80]. Interestingly, some peptides that showed a higher binding free energy score with high DPP-IV inhibitor activity were sourced from egg protein, milk, and salmon hydrolysates [3,41,127,145].…”

“…Nowadays, food components are of great concern because of their high nutritional content and role in the prevention and management of diabetes. Due to the rapid development of potential bioactive compounds from natural sources, food proteins or food-derived peptides have been recognized to play an essential role in regulating blood glucose levels, which is one of the characteristics of diabetes [1][2][3][4]. Numerous studies of potential peptides are being carried out in preclinical trials [5,6].…”

A comprehensive review on the glucoregulatory properties of food-derived bioactive peptides

“…Bovine α-lactalbumin hydrolysates generated by alcalase contain DPP-IV inhibitory peptides, ELKDLKGY and ILDKVGINY. These peptides could form hydrogen bonds, pi-cation interactions, and salt bridges with DPP-IV enzyme as shown by molecular docking studies ( Gao, Gong, & Mao, 2020 ). Camel milk also contains peptides with DPP-IV inhibitory effects, as well as positive effects on insulin receptor activation and glucose uptake ( Ashraf et al, 2021 ).…”