A Novel Angiotensin I-Converting Enzyme Inhibitory Pentapeptide from Red Mold Rice: Identification, Stability, In V i vo Antihypertensive Effects, and Underlying Mechanisms

Abstract Bioactive peptides from fermented food have potential for hypertension management. Red mold rice (RMR), a traditional food made by fermenting rice with Monascus strains, has shown antihypertensive effects. However, research on ACE inhibitory peptides from RMR remains limited. In this study, a novel pentapeptide Val-Leu-Thr-Gly-Trp (VLTGW) was isolated from RMR and displayed potent angiotensin-converting enzyme (ACE) inhibitory activity with an IC50 value of 17.4 μM. VLTGW’s 550-fold selectivity for ACE over renin indicated a potential advantage for reducing off-target effects. VLTGW retained over 90% of its activity across temperatures (20–80 °C) and pH conditions (2.0–12.0). In spontaneously hypertensive rats, VLTGW significantly lowered blood pressure, and this effect was accompanied by reduced ACE activity and angiotensin II levels and increased nitric oxide levels. Overall, these findings identify RMR as a source of an ACE-inhibitory peptide and support further evaluation of VLTGW as a functional food.