A combined in vitro and in silico study of the inhibitory mechanism of angiotensin-converting enzyme with peanut peptides

Jiale Liu; Wentian Song; Xue Gao; Jiaoyan Sun; Chunlei Liu; Li Fang; Ji Wang; Junhua Shi; Yue Leng; Xiaoting Liu; Weihong Min

doi:10.1016/j.ijbiomac.2024.131901

A combined in vitro and in silico study of the inhibitory mechanism of angiotensin-converting enzyme with peanut peptides

Int J Biol Macromol. 2024 Apr 26;268(Pt 2):131901. doi: 10.1016/j.ijbiomac.2024.131901. Online ahead of print.

Authors

Jiale Liu¹, Wentian Song¹, Xue Gao¹, Jiaoyan Sun¹, Chunlei Liu¹, Li Fang¹, Ji Wang¹, Junhua Shi¹, Yue Leng¹, Xiaoting Liu², Weihong Min³

Affiliations

¹ College of Food Science and Engineering, National Engineering Laboratory of Wheat and Corn Deep Processing, Jilin Agricultural University, Changchun 130118, Jilin, China.
² College of Food Science and Engineering, National Engineering Laboratory of Wheat and Corn Deep Processing, Jilin Agricultural University, Changchun 130118, Jilin, China. Electronic address: liuxiaoting@jlau.edu.cn.
³ College of Food Science and Engineering, National Engineering Laboratory of Wheat and Corn Deep Processing, Jilin Agricultural University, Changchun 130118, Jilin, China; College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China. Electronic address: minwh2000@zafu.edu.cn.

PMID: 38677685
DOI: 10.1016/j.ijbiomac.2024.131901

Abstract

Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.

Keywords: Angiotensin-converting enzyme; HUVEC cell; Inhibitor; Molecular dynamics simulation; Peanut peptides.