Identification, structure-activity relationship and in silico molecular docking analyses of five novel angiotensin I-converting enzyme (ACE)-inhibitory peptides from stone fish (Actinopyga lecanora) hydrolysates.

Stone fish is an under-utilized sea cucumber with many health benefits. Hydrolysates with strong ACE-inhibitory effects were generated from stone fish protein under the optimum conditions of hydrolysis using bromelain and fractionated based on hydrophobicity and isoelectric properties of the constituent peptides. Five novel peptide sequences with molecular weight (mw) < 1000 daltons (Da) were identified using LC-MS/MS. The peptides including Ala-Leu-Gly-Pro-Gln-Phe-Tyr (794.44 Da), Lys-Val-Pro-Pro-Lys-Ala (638.88 Da), Leu-Ala-Pro-Pro-Thr-Met (628.85 Da), Glu-Val-Leu-Ile-Gln (600.77 Da) and Glu-His-Pro-Val-Leu (593.74 Da) were evaluated for ACE-inhibitory activity and showed IC50 values of 0.012 mM, 0.980 mM, 1.310 mM, 1.440 mM and 1.680 mM, respectively. The ACE-inhibitory effects of the peptides were further verified using molecular docking study. The docking results demonstrated that the peptides exhibit their effect mainly via hydrogen and electrostatic bond interactions with ACE. These findings provide evidence about stone fish as a valuable source of raw materials for the manufacture of antihypertensive peptides that can be incorporated to enhance therapeutic relevance and commercial significance of formulated functional foods.

Blood-pressure lowering efficacy of winged bean seed hydrolysate in spontaneously hypertensive rats, peptide characterization and a toxicity study in Sprague-Dawley rats.

Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.