Natural ACE-Inhibitor Candidates for Hypertension: A Narrative Literature Review with In Silico Highlights

Abstract

Hypertension remains a major global health burden and is one of the leading risk factors for cardiovascular morbidity and mortality. The renin–angiotensin–aldosterone system, particularly angiotensin-converting enzyme (ACE), plays a central role in blood pressure regulation by catalysing the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor. Therefore, ACE inhibition represents an important therapeutic strategy in hypertension management. This narrative literature review aimed to summarise and critically discuss the potential of natural bioactive compounds as ACE inhibitor candidates, with particular emphasis on evidence derived from in silico and molecular docking studies. Relevant peer-reviewed articles were reviewed by focusing on natural compounds, including flavonoids, phenolic compounds, bioactive peptides, chlorogenic acid, quercetin, luteolin derivatives, fucoidan, scopoletin, and folate. Several natural compounds demonstrated favourable binding affinity and interaction patterns with ACE active sites in computational studies. Chlorogenic acid, quercetin, luteolin derivatives, scopoletin, fucoidan, phenolic compounds, and selected bioactive peptides showed potential molecular interactions comparable to standard ACE inhibitors in several docking analyses. However, most available evidence remains predictive and should be interpreted as binding propensity rather than confirmed enzymatic inhibition or clinical antihypertensive efficacy. Natural bioactive compounds represent promising molecular scaffolds for the development of ACE inhibitor candidates in hypertension therapy. Nevertheless, further validation through in vitro enzymatic assays, kinetic inhibition studies, toxicity evaluation, and in vivo pharmacological assessment is required to confirm their biological relevance and therapeutic applicability.