Integrated network pharmacology and experimental validation to explore the mechanisms of Coregonus peled-derived myosin ACE-inhibiting peptides for the treatment of hypertension

Yabo Wei; Zhouping Wang; Xin Guo; Yongdong Lei; Xiaorong Deng; Jian Zhang

doi:10.1016/j.ijbiomac.2024.138218

Integrated network pharmacology and experimental validation to explore the mechanisms of Coregonus peled-derived myosin ACE-inhibiting peptides for the treatment of hypertension

Int J Biol Macromol. 2024 Nov 29:138218. doi: 10.1016/j.ijbiomac.2024.138218. Online ahead of print.

Authors

Yabo Wei¹, Zhouping Wang¹, Xin Guo¹, Yongdong Lei², Xiaorong Deng³, Jian Zhang⁴

Affiliations

¹ School of Food Science and Technology, Shihezi University, Shihezi 832003, Xinjiang, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty(Co-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China.
² Food Quality and Testing Center of Ministry of Agriculture and Rural Affairs, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, Xinjiang 832000, China.
³ School of Food Science and Technology, Shihezi University, Shihezi 832003, Xinjiang, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty(Co-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China. Electronic address: dengxr22@shzu.edu.cn.
⁴ School of Food Science and Technology, Shihezi University, Shihezi 832003, Xinjiang, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty(Co-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China; Key Laboratory for Food Nutrition and Safety Control of Xinjiang Production and Construction Corps, School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832003, China. Electronic address: zhangjian0411@163.com.

PMID: 39617224
DOI: 10.1016/j.ijbiomac.2024.138218

Abstract

Coregonus peled is rich in protein and is a plentiful resource of bioactive peptides. This study was aimed at extracting novel Angiotensin I-converting enzyme (ACE) inhibitory peptides from Coregonus peled and revealing their potential hypotensive mechanisms. This paper screened six ACE inhibitory peptides with high bioactivity, good water solubility, and ADMET properties by computerized enzyme digestion of myosin-heavy chain from Coregonus peled, and LCYPR had the greatest ACE inhibition activity (IC₅₀ = 47.8782 μM). There were 47 potentially critical targets of LCYPR for hypertension treatment, involving 135 biological processes (BP), 30 cellular components (CC), and 30 molecular functions (MF). The results of KEGG pathway analyse showed that the LCYPR participated in 50 pathways including the renin-angiotensin system, renin secretion, lipid and atherosclerosis, relaxin signaling pathway, IL-17 signaling pathway, atherosclerosis, fluid shear stress, and others, through the key targets such as AGT, AKT1, ACE, REN, CTSB, STAT3, PLG, SRC, MMP2, and F2 to regulate the blood pressure of organisms. In conclusion, the study obtained a novel ACE inhibitory peptide from the myosin-heavy chain of Coregonus peled and revealed the potential target and pathway of LCYPR to improve hypertension. The study provides new ideas and methods for developing novel antihypertensive peptides. The results provide a theoretical basis for developing functional foods of the Xinjiang specialty cold-water fish.

Keywords: Angiotensin I-converting enzyme; Coregonus peled-derived myosin; Network pharmacology.