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ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Food Science Technology
Volume 12 - 2025 |
doi: 10.3389/fnut.2025.1528184
In vitro Gastrointestinal Digestion Simulation Screening of Novel ACEI Peptides from Broccoli: Mechanism in High Glucose-Induced VSMCs Dysfunction
Provisionally accepted
Shuzhi Zhang
1*
Jingjing Guo
2
Shikun Suo
3*
Li Ju
1
Zhaoqiang Jiang
1
Pingshuan Dong
2*
Yanli Wang
3*
Yali Dang
3*
Laijing Du
2*- 1 Hangzhou Medical College, Hangzhou, Zhejiang Province, China
- 2 The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
- 3 Ningbo University, Ningbo, China
Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking,. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42 % after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level > 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels.Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases.
Keywords: Gastrointestinal digestion simulation, ACEI peptides, Broccoli, VSMCs, Ang II, ACE2
Received: 14 Nov 2024; Accepted: 06 Jan 2025.
Copyright: © 2025 Zhang, Guo, Suo, Ju, Jiang, Dong, Wang, Dang and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shuzhi Zhang, Hangzhou Medical College, Hangzhou, 310053, Zhejiang Province, China
Shikun Suo, Ningbo University, Ningbo, China
Pingshuan Dong, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
Yanli Wang, Ningbo University, Ningbo, China
Yali Dang, Ningbo University, Ningbo, China
Laijing Du, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
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