Chicoric acid-rich extract of Cichorium intybus seeds (CAREOCI) preserves pancreatic β-cell function under glucotoxic stress through modulation of MAFA, DYRK1A, cell cycle, apoptosis, and mitochondrial dysfunction

Introduction Progressive decline in functional pancreatic β-cell mass is a key pathological feature of type 2 diabetes mellitus (T2DM), highlighting the need for therapies that preserve and regenerate β-cells. This study investigated the preservative effects of a chicoric acid-rich aqueous extract of Cichorium intybus seeds (CAREOCI) under glucotoxic conditions (25 mM glucose) in pancreatic β-cells. Methods Phytochemical standardisation by HPTLC, HPLC, and LC–MS/MS confirmed chicoric acid is the principal constituent present in CAREOCI. A molecular docking study identified DYRK1A is a one of the key target (−8.72 kcal/mol) of chicoric acid for β-cell regeneration. In glucotoxic MIN 6 β-cells, CAREOCI significantly enhanced glucose-stimulated insulin secretion, restored antioxidant status, reduced intracellular ROS, and suppressed IL-1β and TNF-α. Results CAREOCI also reduced apoptosis, attenuated caspase-3/7 activity, preserved normal nuclear morphology, restored mitochondrial membrane potential, and promoted autophagy through increased acidic vesicular organelles. Cell-cycle analysis indicated a trend toward increased S-phase population, suggesting enhanced β-cell proliferation. At the molecular level, CAREOCI downregulated DYRK1A, NF-κB, mTOR, and CHOP while upregulating MAFA, PDX1, PAX6, and NKX6.1, supporting β-cell survival and preservation. Compared with purified chicoric acid, CAREOCI consistently exhibited greater efficacy, indicating potential complementarity among its phytoconstituents. Conclusion CAREOCI protects pancreatic β-cells through coordinated antioxidant, anti-inflammatory, anti-apoptotic, mitochondrial-protective, autophagy-promoting effects, supporting beta cell preservation and function under glucotoxicity condition supporting its potential as a phytopharmaceutical for T2DM.