Ribeiro-Oliveira Rita, Martins Zita E, Faria Miguel Ângelo, Sousa Joana Beatriz, Ferreira Isabel M P L V O, Diniz Carmen
LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
LAQV/REQUIMTE, Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Life (Basel). 2022 Oct 7;12(10):1554. doi: 10.3390/life12101554.
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.
高血压的治疗对于降低心血管疾病风险至关重要，心血管疾病是全球主要死因。血管紧张素转换酶（ACE）抑制剂是一类具有多种副作用的抗高血压药物。天然产物，即来自酿造副产品、啤酒糟（BSG）和酵母（BSY）的生物活性肽，是有前景的替代品，因为它们在体外可抑制ACE。然而，由于活性肽的生物利用度可能发生变化，口服这些肽可能会改变其预期的抑制作用，而这一点迄今尚未得到评估。本研究的目的是通过将蛋白质水解物依次进行模拟胃肠消化、肠道吸收（Caco-2细胞）和肝脏代谢（HepG2细胞）来模拟口服给药，以评估BSG/BSY肽的有效性。采用MTT法评估BSG/BSY蛋白质水解物的安全性。使用荧光法检测初始和最终蛋白质水解物（BSY、BSG和一种新产品MIX）的ACE抑制潜力，并与卡托普利（1 µM，一种ACE抑制药物）进行比较。口服给药模拟大大提高了BSY和MIX蛋白质水解物的ACE抑制能力，尽管最终的MIX和BSG显示出比卡托普利更强的ACE抑制潜力。尽管如此，所有最终蛋白质水解物均具有ACE抑制能力，因此是治疗高血压的有前景的化合物。
