From discarded by-product to functional bioactive: Date seed extracts reverse pancreatic β-cell dysfunction via multi-pathway regulation in diabetic rats

The exploration of natural products capable of addressing both the molecular and functional aspects of β-cell failure is imperative given the increasing morbidity and mortality of diabetes mellitus. Our study investigated the effectiveness of ethanolic extracts of various date seed varieties in streptozotocin-induced diabetic rat model. The supplementation, especially of Mazafati and Zahidi seeds extracts, significantly improved the glycemic index. They also exhibited improved serum insulin and C-peptide levels, reduced oxidative stress, and normalized lipid and protein profiles. The qRT-PCR results also revealed corresponding changes in calcium signaling and MAPK/JNK, TRAF-mediated inflammation, FOXO-2, and JAK-STAT pathways, supporting β-cells regeneration and function. Histopathological analysis further confirmed the partial restoration of islet structure and β-cell mass in the treatment groups. These findings indicate that date seed extracts feature promising bioactive compounds that can reverse β-cell dysfunction through integrated molecular mechanisms. These findings also suggest the potential of developing standardized functional food interventions. • Date seed extract exhibits strong antioxidant and antidiabetic effects. • Date seed extract reduces oxidative stress and promotes pancreatic regeneration. • Date seed phytochemicals enhance pancreatic β-cell function and insulin secretion. • Phenolic and flavonoid compounds in date seeds mediate glucose-lowering effects.