Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from seaweed represent a potential source of new antihypertensive. The aim of this study was to isolate and purify ACE inhibitory peptides (ACEIPs) from the protein hydrolysate of the marine macroalga Ulva intestinalis. U. intestinalis protein was hydrolyzed by five different proteases (trypsin, pepsin, papain, α-chymotrypsin, alcalase) to prepare peptides; compared with other hydrolysates, the trypsin hydrolysates exhibited the highest ACE inhibitory activity. The hydrolysis conditions were further optimized by response surface methodology (RSM), and the optimum conditions were as follows: pH 8.4, temperature 28.5 °C, enzyme/protein ratio (E/S) 4.0%, substrate concentration 15 mg/mL, and enzymolysis time 5.0 h. After fractionation and purification by ultrafiltration, gel exclusion chromatography and reverse-phase high-performance liquid chromatography, two novel purified ACE inhibitors with IC₅₀ values of 219.35 μM (0.183 mg/mL) and 236.85 μM (0.179 mg/mL) were obtained. The molecular mass and amino acid sequence of the ACE inhibitory peptides were identified as Phe-Gly-Met-Pro-Leu-Asp-Arg (FGMPLDR; MW 834.41 Da) and Met-Glu-Leu-Val-Leu-Arg (MELVLR; MW 759.43 Da) by ultra-performance liquid chromatography-tandem mass spectrometry. A molecular docking study revealed that the ACE inhibitory activities of the peptides were mainly attributable to the hydrogen bond and Zn(II) interactions between the peptides and ACE. The results of this study provide a theoretical basis for the high-valued application of U. intestinalis and the development of food-derived ACE inhibitory peptides.

Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL is detrimental to tumors, we purified PGL to characterize its chemical composition, molecular weight, and sugar and protein content and investigated its antitumor activity. We demonstrated that PGL exerted its antitumor activities by modulating cell viability, morphology, apoptosis, and the apoptosis-related Fas/FasL signaling pathway in the human lung cancer cell line A549, the gastric cancer cell line MKN28, and the mouse melanoma cell line B16. Our data provide the first evidence that PGL inhibits cell proliferation by inducing apoptosis, which is largely mediated by Fas/FasL in cancer cells, suggesting that PGL might be a novel therapeutic agent against cancer.