Mechanisms and Production of Hypoglycaemic Peptides: Exploring the Potential of Chlamydomonas reinhardtii.

Abstract

Diabetes, particularly type 2 diabetes mellitus (T2DM), has emerged as a major global health challenge, while currently available therapeutic drugs are frequently associated with drug resistance and adverse side effects. In recent years, bioactive peptides have attracted increasing attention as promising hypoglycaemic candidates due to their favorable safety profiles, good tolerability, and multi-target physiological regulatory activities. As a GRAS-designated unicellular green alga, Chlamydomonas reinhardtii is characterized by a high protein content, with approximately 46.9% of its dry biomass composed of protein, making it a rich source for the development of hypoglycaemic short peptides. Previous studies have shown that proteolytic products derived from C. reinhardtii markedly inhibit key glucose-regulating enzymes, including α-amylase and α-glucosidase, exhibiting superior inhibitory potential compared with various terrestrial protein sources. Nevertheless, challenges remain in the large-scale production of C. reinhardtii-derived hypoglycaemic peptides, precise control of the proteolytic process, and validation of their in vivo efficacy. This review summarizes the major sources of hypoglycaemic peptides, current extraction and characterization strategies, and their underlying mechanisms of action, while highlighting the application potential and key limitations of C. reinhardtii-derived hypoglycaemic peptides. Addressing these challenges is expected to facilitate the development and application of C. reinhardtii-based functional foods and nutraceuticals for diabetes management.