Zhao Yuxin, Cui Huimin, Lin Hong, Gong Wei, Li Na, Yang Jianjun
School of Public Health, Ningxia Medical University, Yinchuan 750004, China.
Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750004, China.
J Agric Food Chem. 2025 Aug 13;73(32):20149-20162. doi: 10.1021/acs.jafc.5c01994. Epub 2025 Jul 30.
This study aimed to identify the sequence and assess the stability of angiotensin-converting enzyme (ACE) inhibitory peptides derived from ultrafine pomace powder (u-LPP), while network pharmacology analysis was employed to explore potential mechanisms for heart failure with preserved ejection fraction (HFpEF) improvement. The peptides identified by LC-MS/MS were GPFN, LGGP, AGLP, and TAFP, among which GPFN had the highest activity (IC of 324.44 ± 8.93 μM). GPFN exhibits gastrointestinal enzyme hydrolysis resistance. Furthermore, after 2 h of incubation, GPFN could permeate Caco-2 cell monolayers through the paracellular route by passive diffusion. Molecular docking revealed that GPFN could stably bind to ACE (binding energy of -8.88 kcal/mol). Molecular dynamics (MD) simulation indicated that the ACE-GPFN complex had good stability. Network pharmacological analysis and molecular docking demonstrated strong interactions between GPFN and key targets, such as CASP3, MMP9, SRC, APP, ACE, and MMP2. GPFN might have the potential activity to improve HFpEF.
本研究旨在鉴定源自超细果渣粉（u-LPP）的血管紧张素转换酶（ACE）抑制肽的序列并评估其稳定性，同时采用网络药理学分析来探索改善射血分数保留的心力衰竭（HFpEF）的潜在机制。通过LC-MS/MS鉴定出的肽为GPFN、LGGP、AGLP和TAFP，其中GPFN活性最高（IC为324.44±8.93μM）。GPFN表现出对胃肠道酶水解的抗性。此外，孵育2小时后，GPFN可通过被动扩散经细胞旁途径穿过Caco-2细胞单层。分子对接显示GPFN可与ACE稳定结合（结合能为-8.88 kcal/mol）。分子动力学（MD）模拟表明ACE-GPFN复合物具有良好的稳定性。网络药理学分析和分子对接证明GPFN与关键靶点如CASP3、MMP9、SRC、APP、ACE和MMP2之间存在强烈相互作用。GPFN可能具有改善HFpEF的潜在活性。
