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
4 affiliations
- 1Hamdard Institute of Medical Sciences and Research (HIMSR) , ,
- 2Jamia Hamdard School of Chemical and Life Sciences , ,
- 3Jamia Hamdard School of Pharmaceutical Education and Research , ,
- 4ICMR - National Institute of Cancer Prevention and Research , ,
Abstract
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.
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BibTeX
@article{khan2026chicoric,
title = {{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}},
author = {Anish Murtaja Alam Khan and Kailash Chandra and Furqan Choudhary and Aftab Alam and Farheen Azad and Jasmeet Kaur and Mohit Suyal and Yasmin Bano and Dinesh Kumar Singhal and Sayeed Ahmad and Bibhu Prasad Panda and Vineet Jain},
journal = {Frontiers in pharmacology},
year = {2026},
month = sep,
doi = {10.3389/fphar.2026.1953632},
url = {https://europepmc.org/article/PMC/PMC13661457},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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
AU - Anish Murtaja Alam Khan
AU - Kailash Chandra
AU - Furqan Choudhary
AU - Aftab Alam
AU - Farheen Azad
AU - Jasmeet Kaur
AU - Mohit Suyal
AU - Yasmin Bano
AU - Dinesh Kumar Singhal
AU - Sayeed Ahmad
AU - Bibhu Prasad Panda
AU - Vineet Jain
PY - 2026
DA - 2026/09/30
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1953632
UR - https://europepmc.org/article/PMC/PMC13661457
AB - 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.
SN - 1663-9812
ER -