A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Abstract

Alcalase, neutral protease, and pepsin were used to hydrolyze the skin of Takifugu flavidus. The T. flavidus hydrolysates (TFHs) with the maximum degree of hydrolysis (DH) and angiotensin-I-converting enzyme (ACE)-inhibitory activity were selected and then ultra-filtered to obtain fractions with components of different molecular weights (MWs) (<1, 1–3, 3–10, 10–50, and >50 kDa). The components with MWs < 1 kDa showed the strongest ACE-inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.58 mg/mL. Purification and identification using semi-preparative liquid chromatography, Sephadex G-15 gel chromatography, RP-HPLC, and LC–MS/MS yielded one new potential ACE-inhibitory peptide, PPLLFAAL (non-competitive suppression mode; IC50 of 28 μmmol·L−1). Molecular docking and molecular dynamics simulations indicated that the peptides should bind well to ACE and interact with amino acid residues and the zinc ion at the ACE active site. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that PPLLFAAL could significantly decrease the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHRs after intravenous administration. These results suggested that PPLLFAAL may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.

Isolation, identification, molecular docking analysis, and cytoprotection of seven novel angiotensin I-converting enzyme inhibitory peptides from miiuy croaker byproducts-swim bladders

“…Therefore, ultrafiltration process often serves to collect small MW bioactive peptides from protein hydrolysates (Abdelhedi et al, 2017). The current findings agreed with the reports that the lowest MW fractions of hydrolysates from Moringa oleifera leaf (Ma et al, 2021), tuna black muscle (Qiao et al, 2022) and frame (Lee et al, 2010), smooth-hound viscera (Abdelhedi and Nasri, 2019), Antarctic krill (Zhao et al, 2019b), Cyclina sinensis (Yu et al, 2018), and Takifugu flavidus skin (Su et al, 2021) presented the highest ACEi activities. Then, MSCH-I was selected for the next step isolation.…”

“…proved that peptides with four to nine amino acid residues could passively pass through cell membranes to play their functions in cells (Su et al, 2021). In the experiment, MMP3 (SHGEY) and MMP6 (SPYGF) are pentapeptides, and the MWs increase their access to the active site of ACE, which was proved by their affinities with ACE (-8.7 and -9.7 kcal/mol for MMP3 and MMP6, respectively).…”

“…In the experiments on spontaneously hypertensive rats (SHRs), corn germ ACEi peptide with IC 50 of 0.83 mg/mL could markedly lower the systolic BP, adjust the level of relaxing and contracting factors derived by endothelium in serum, and suppress the ACE activities in different organs (Guo et al, 2020). PPLLFAAL with IC 50 of 28 mmmol/L could remarkably reduce the systolic BP and diastolic BP of SHRs after intravenous administration (Su et al, 2021). Similarly, LGF and GLFF from leaf hydrolysate of Moringa oleifera exhibited double inhibitory activity of ACE and renin and significantly reduced the systolic and diastolic BP of SHRs (Ma et al, 2021).…”

Isolation, identification and in vivo antihypertensive effect of novel angiotensin I-converting enzyme (ACE) inhibitory peptides from Spirulina protein hydrolysate

“…2,3 ACE is a dipeptidyl carboxypeptidase belonging to the zinc metalloenzyme family; 4 it plays a vital role in the rein-angiotensin system (RAS) and kallikrein-kinin system (KKS), which are two key mechanisms involved in regulating blood pressure within our body. Briefly, two amino acid residues of angiotensinogen are cut off by renin to form angiotensin (1)(2)(3)(4)(5)(6)(7)(8)(9), also known as Ang I. Then, two amino acid residues of Ang I are further cut off by ACE, forming angiotensin (1-7) (Ang II).…”

Preparation of angiotensin I-converting enzyme (ACE) inhibitory peptides from Tie Guanyin tea residue protein using two-step enzymatic hydrolysis

“…ACE inhibitory peptide can bind to the active center of ACE, inhibiting the activity of ACE and lowering blood pressure. ACE inhibitory peptide of natural origin is more effective than traditional antihypertensive drugs, without toxic side effects, and has no effect on normal blood pressure, which is important for the treatment of hypertension and human health (Su et al, 2021).…”