Plant-derived angiotensin-converting enzyme regulatory peptides: Potential sources, mechanisms and applications

Angiotensin-converting enzyme (ACE) is mainly categorized into ACE-1 and ACE-2, both of which play significant roles in human physiological balance and metabolism. Compared to synthetic drugs, food-derived natural peptides offer unique advantages regarding safety and applicability in various scenarios. In recent years, a large number of ACE regulatory peptides including ACE inhibitory peptides and ACE-2 up-regulatory peptides originated from plant sources, have been identified. This review aimed to summarize the different characteristics of ACE and its role in homeostasis and diseases, the different plant sources of ACE regulatory peptides. The preparation methods, activity assays and physiological regulation mechanisms of peptides are addressed in the meantime. In addition, emerging tools for optimizing the activity of peptides are highlighted. Artificial intelligence tools can facilitate activity prediction for rapid screening and validation, as well as assist in designing peptides with higher activity, while high-throughput activity validation matches the expanding library of ACE regulatory peptide candidates. In the next generation of personalized nutritional interventions, it is crucial to overcome the bioavailability bottleneck by achieving precise delivery through chemical modifications and other methods. Meanwhile, novel technologies represented by organoids and organ-on-a-chip devices can simulate multi-organ interactions, reduce the heavy burden of in vivo experiments. The future of functional foods or adjuvant therapeutic drugs utilizing plant-derived ACE regulatory peptides is promising. This review provides a comprehensive understanding of the underlying mechanisms, emerging technologies, and serves as a practical guide for the research, production, and even commercial applications.