RESUMEN
BACKGROUND: Nutraceuticals have been important for more than two decades for their safety, efficacy, and outstanding effects. Diabetes is a major metabolic syndrome, which may be improved using nutritional pharmaceuticals. Some microalgae species, such as spirulina, stand out by providing biomass with exceptional nutritional properties. Spirulina has a wide range of pharmacological effects, mostly related to phycocyanin. Phycocyanin is a protein compound with antidiabetic properties, known as a nutraceutical. OBJECTIVE: This review delves into phycocyanin applications in diabetes and its complications and ascertains the mechanisms involved. METHODS: Scopus, PubMed, Cochrane Library, Web of Science, and ProQuest databases were systematically reviewed (up to April 30, 2023), in which only animal and cellular studies were found. RESULTS: According to animal studies, the administration of phycocyanin affected biochemical parameters (primary outcome) related to diabetes. These results showed an increase in fasting insulin serum and a decrease in fasting blood glucose, glycosylated serum protein, and glycosylated hemoglobin. In cellular studies, though, phycocyanin prevented methylglyoxal and human islet amyloid polypeptide-induced dysfunction in ß-cells and induced apoptosis through different molecular pathways (secondary outcome), including activation of Nrf2, PI3K/Akt, and suppression of JNK and p38. Also, phycocyanin exerted its antidiabetic effect by affecting the pathways regulating hepatic glucose metabolism. CONCLUSIONS: Thus, based on the available information and literature, targeting these pathways by phycocyanin may unleash an array of benefits, including positive outcomes of the antidiabetic effects of phycocyanin as a nutraceutical. OTHER: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) at the National Institute of Health. The registration number is CRD42022307522.