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.

Authors

Anish Murtaja Alam Khan, Kailash Chandra, Furqan Choudhary, Aftab Alam, Farheen Azad, Jasmeet Kaur, Mohit Suyal, Yasmin Bano, Dinesh Kumar Singhal, Sayeed Ahmad, Bibhu Prasad Panda, Vineet Jain

Published in

Frontiers in pharmacology. Volume 17. Pages 1953632. Epub Sep 30, 2026.

Abstract

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.
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.
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.
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.

PMID:
42876685
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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