Protein Hydrolysates from Brewing By-Products as Natural Alternatives to ACE-Inhibitory Drugs for Hypertension Management

SIMPLE SUMMARY: Hypertension is the predominant risk factor for cardiovascular disease, which is the leading cause of mortality and morbidity worldwide. The search for natural compounds with antihypertensive properties, such as bioactive peptides from brewing by-products (spent grain and yeast), which are less likely to cause severe side effects compared with anti-hypertensive drugs, is of major importance to reduce cardiovascular events. Since oral intake of these peptides may modify their expected effects, the aim of the present study was to simulate oral administration and evaluate the impact of gastrointestinal digestion, intestinal absorption, and liver metabolism on the effectiveness of those bioactive peptides and determine their potential to be used as supplements or nutraceuticals as well as anti-hypertensive drugs before moving forward to animal studies. Results showed that peptides derived from the brewing industry maintain or present higher antihypertensive activity after simulation of oral administration, validating the usefulness of these peptides to reduce the risk, ameliorate, or treat primary hypertension. In conclusion, this study reinforces, through in vitro studies, the benefits of oral administrated brewing bioactive peptides to directly manage hypertension by lowering blood pressure, thus being promising compounds. ABSTRACT: The treatment of hypertension is of major importance to reduce the risk of cardiovascular disease, the leading cause of death worldwide. Angiotensin-converting enzyme (ACE) inhibitors are anti-hypertensive drugs associated with several side effects. Natural products, namely bioactive peptides from brewing by-products, brewers’ spent grain (BSG), and yeast (BSY), are promising alternatives since they can inhibit ACE in vitro. However, the oral intake of these peptides may modify their expected inhibitory effect owing to possible changes in active peptides’ bioavailability, which have not been assessed so far. The goal of this study was to simulate oral administration to evaluate BSG/BSY peptides’ effectiveness by submitting protein hydrolysates sequentially to simulated gastrointestinal digestion, intestinal absorption (Caco-2 cells), and liver metabolism (HepG2 cells). MTT assay was used to assess BSG/BSY protein hydrolysates safeness. The ACE-inhibitory potential of initial and final protein hydrolysates (BSY, BSG, and a new product, MIX) were tested using a fluorometric assay and compared with captopril (1 µM, an ACE-inhibitory drug). Simulation of oral administration greatly increased BSY and MIX protein hydrolysates’ ACE-inhibitory capacity, though final MIX and BSG revealed greater ACE-inhibitory potential than captopril. Notwithstanding, all final protein hydrolysates presented ACE-inhibitory capacity, thus being promising compounds to manage hypertension.