ACE Inhibitory Peptide from Skin Collagen Hydrolysate of Takifugu bimaculatus as Potential for Protecting HUVECs Injury

Angiotensin-I-converting enzyme (ACE) is a crucial enzyme or receptor that catalyzes the generation of potent vasopressor angiotensin II (Ang II). ACE inhibitory peptides from fish showed effective ACE inhibitory activity. In this study, we reported an ACE inhibitory peptide from Takifugu bimaculatus (T. bimaculatus), which was obtained by molecular docking with acid-soluble collagen (ASC) hydrolysate of T. bimaculatus. The antihypertensive effects and potential mechanism were conducted using Ang-II-induced human umbilical vein endothelial cells (HUVECs) as a model. The results showed that FNLRMQ alleviated the viability and facilitated apoptosis of Ang-II-induced HUVECs. Further research suggested that FNLRMQ may protect Ang-II-induced endothelial injury by regulating Nrf2/HO-1 and PI3K/Akt/eNOS signaling pathways. This study, herein, reveals that collagen peptide FNLRMQ could be used as a potential candidate compound for antihypertensive treatment, and could provide scientific evidence for the high-value utilization of marine resources including T. bimaculatus.

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

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.

Optimization of Enzymatic Extraction of ACE Inhibitory Peptide from Rohu (Labeo rohita) Fish Waste using RSM

Background: Hypertension is one of the cardiovascular disease that kills people silently across the globe. It can be controlled, in one of the way, by ACE inhibitory peptide extracted from aquatic resources. Methods: Rohu (Labeo rohita) fish wastes were quantified for their anatomical yield; analyzed for their proximate composition and optimized the enzymatic extraction parameters for ACE inhibitory peptides. Response surface methodology with Box-Benhken Design (RSM-BBD) was used to optimize alcalase concentration (0.5-2% v/w), hydrolysis temperature (45-60°C), hydrolysis time (60-240 min.) and solid: liquid (S/L) ratio (0.2-1) to obtain rohu fish waste peptides. Results: More waste generated in smaller (49.4%) than medium and bigger (34.5%) fish. Quantum of edible flesh (59.06%) was followed by head (23.9%), trimmings (5.18%), scales (4.19%) and swim bladder (0.65%). However, protein content was highest in swim bladder (34.1%) followed by scales (22.9%), trimmings (18.7%) and head (17.1%). Alcalase concentration (1.08%, v/w), temperature (52.10°C), hydrolysis time (129.18 min) and S/L ratio (0.8:1) were found optimum for extraction ACE inhibitory peptide with DH, ACE inhibition and PY of 19.27%, 54.98% and 51.37% respectively. Results showed the potential of extracted ACE inhibitory peptide as ingredients in functional food.