Pheophytin a from Microcystis aeruginosa exerts antidiabetic activity in streptozotocin-induced diabetes in rat model

Microcystis aeruginosa is increasingly recognized as a valuable microbial source of bioactive secondary metabolites; however, the biotechnological potential of its pigments as antidiabetic agents remains largely unexplored. This study aimed to valorize M. aeruginosa biomass by isolating five major pigment derivatives and evaluating their antidiabetic activity in a streptozotocin-induced diabetic rat model. The algal extract was prepared, and five major compounds were separated, purified, and were identified. The two compounds, 1 and 5, were identified by their full spectral data as Dihydroxychlorophyllide a and Pheophytin a. The remaining three purified compounds, 2, 3, and 4, were identified based on their 1H- and 13C-NMR and ESI–MS data, as Chlorophyll-a, Hydroxypheophytin, and Anthraxanthin. Crucially, these isolated pigment fractions were determined to be non-toxic. Their antidiabetic effect on streptozotocin-induced diabetes was assessed in rat model with emphasis on blood glucose regulation, insulin receptor expression, GLUT4 levels, PI3K/AKT signaling, PKC/MAPK activity, and inflammatory biomarkers. Treatment with the isolated metabolites, particularly Pheophytin a, significantly mitigated hyperglycemia, upregulated insulin receptor and GLUT4 expression, activated the PI3K/AKT signaling pathway, and suppressed TNF-α mediated inflammation. Histological analysis confirmed that Compounds 2, 3, and 5 effectively preserved pancreatic architecture and protected Islets of Langerhans from diabetic atrophy and fibrosis. These findings demonstrate the novelty of identifying potent antidiabetic activity in M. aeruginosa pigments and support the biotechnological relevance of this cyanobacterium as a safe producer of bioactive metabolites for therapeutic applications.