{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:04:32Z","timestamp":1790744672993,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Progressive decline in functional pancreatic \u03b2-cell mass is a key pathological feature of type 2 diabetes mellitus (T2DM), highlighting the need for therapies that preserve and regenerate \u03b2-cells. This study investigated the preservative effects of a chicoric acid-rich aqueous extract of\n                      <jats:italic>Cichorium intybus<\/jats:italic>\n                      seeds (CAREOCI) under glucotoxic conditions (25 mM glucose) in pancreatic \u03b2-cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Phytochemical standardisation by HPTLC, HPLC, and LC\u2013MS\/MS confirmed chicoric acid is the principal constituent present in CAREOCI. A molecular docking study identified DYRK1A is a one of the key target (\u22128.72 kcal\/mol) of chicoric acid for \u03b2-cell regeneration. In glucotoxic MIN 6 \u03b2-cells, CAREOCI significantly enhanced glucose-stimulated insulin secretion, restored antioxidant status, reduced intracellular ROS, and suppressed IL-1\u03b2 and TNF-\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u03b2-cell proliferation. At the molecular level, CAREOCI downregulated DYRK1A, NF-\u03baB, mTOR, and CHOP while upregulating MAFA, PDX1, PAX6, and NKX6.1, supporting \u03b2-cell survival and preservation. Compared with purified chicoric acid, CAREOCI consistently exhibited greater efficacy, indicating potential complementarity among its phytoconstituents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CAREOCI protects pancreatic \u03b2-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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1953632","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:49:10Z","timestamp":1790743750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chicoric acid-rich extract of Cichorium intybus seeds (CAREOCI) preserves pancreatic \u03b2-cell function under glucotoxic stress through modulation of MAFA, DYRK1A, cell cycle, apoptosis, and mitochondrial dysfunction"],"prefix":"10.3389","volume":"17","author":[{"given":"Anish Murtaja Alam","family":"Khan","sequence":"first","affiliation":[{"name":"Hamdard Institute of Medical Sciences and Research (HIMSR)","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Chandra","sequence":"additional","affiliation":[{"name":"Hamdard Institute of Medical Sciences and Research (HIMSR)","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furqan","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Chemical and Life Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab","family":"Alam","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Pharmaceutical Education and Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farheen","family":"Azad","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Pharmaceutical Education and Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmeet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Pharmaceutical Education and Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Suyal","sequence":"additional","affiliation":[{"name":"Hamdard Institute of Medical Sciences and Research (HIMSR)","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Bano","sequence":"additional","affiliation":[{"name":"ICMR - National Institute of Cancer Prevention and Research","place":["Noida, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh Kumar","family":"Singhal","sequence":"additional","affiliation":[{"name":"ICMR - National Institute of Cancer Prevention and Research","place":["Noida, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayeed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Pharmaceutical Education and Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibhu Prasad","family":"Panda","sequence":"additional","affiliation":[{"name":"Jamia Hamdard School of Pharmaceutical Education and Research","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Jain","sequence":"additional","affiliation":[{"name":"Hamdard Institute of Medical Sciences and Research (HIMSR)","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cmet.2017.08.007","article-title":"Pancreatic \u03b2 cell regeneration as a possible therapy for diabetes","volume":"27","author":"Aguayo-Mazzucato","year":"2018","journal-title":"Cell Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the \u03b2 cell: the last ten years","volume":"148","author":"Ashcroft","year":"2012","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.jep.2013.09.046","article-title":"Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): a comparative in vitro study with the effects of caffeic and ferulic acids","volume":"150","author":"Azay-Milhau","year":"2013","journal-title":"J. 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