{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:34Z","timestamp":1792789774271,"version":"4.5.0"},"reference-count":222,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81903876"],"award-info":[{"award-number":["81903876"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82003985"],"award-info":[{"award-number":["82003985"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973712"],"award-info":[{"award-number":["81973712"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82004030"],"award-info":[{"award-number":["82004030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013061","name":"Jilin Scientific and Technological Development Program","doi-asserted-by":"publisher","award":["20240101215JC"],"award-info":[{"award-number":["20240101215JC"]}],"id":[{"id":"10.13039\/501100013061","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Research Project of Jilin Provincial Department of Education","award":["JJKH20241040KJ"],"award-info":[{"award-number":["JJKH20241040KJ"]}]},{"name":"Project of jilin Provincial Development and Reform Commission","award":["2023C027-3"],"award-info":[{"award-number":["2023C027-3"]}]},{"name":"National College Students\u2019 Innovation and Entrepreneurship Training Program","award":["S202410199095X"],"award-info":[{"award-number":["S202410199095X"]}]},{"name":"National College Students\u2019 Innovation and Entrepreneurship Training Program","award":["S202410199012"],"award-info":[{"award-number":["S202410199012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance and pancreatic \u03b2-cell dysfunction, posing a substantial global health challenge. This review systematically summarizes the therapeutic potential of berberine, a natural isoquinoline alkaloid, in the management of T2DM. Berberine\u2019s pharmacological activities are discussed from multiple perspectives, including enhancing insulin sensitivity and regulating glucose metabolism\u2014encompassing glycogen synthesis, gluconeogenesis, and glucose transport. The review also highlights berberine\u2019s anti-inflammatory, antioxidant, and epigenetic enzyme-targeting actions and its involvement in key T2DM-related signaling pathways such as AKT, AMPK, and GLUTs. These findings collectively elucidate the multi-targeted and multi-pathway molecular mechanisms underlying berberine\u2019s efficacy against T2DM. Additionally, the review covers the pharmacological activities and molecular mechanisms of berberine in treating T2DM complications\u2014including diabetic nephropathy, retinopathy, cardiomyopathy, neuropathy, and diabetic foot ulcers\u2014as well as its clinical and preclinical applications and the synergistic benefits of combination therapy with agents such as metformin, ginsenoside Rb1, and probiotics. By systematically reviewing the literature retrieved from PubMed and Web of Science up to 2025, this article provides a comprehensive summary of current research, offering a theoretical foundation for the clinical use of berberine in T2DM therapy.<\/jats:p>","DOI":"10.3390\/ph18121890","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:11:23Z","timestamp":1765793483000},"page":"1890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Berberine: A Rising Star in the Management of Type 2 Diabetes\u2014Novel Insights into Its Anti-Inflammatory, Metabolic, and Epigenetic Mechanisms"],"prefix":"10.3390","volume":"18","author":[{"given":"Da","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donglu","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Clinical Medical, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"M\u0142ynarska, E., Czarnik, W., Dzie\u017ca, N., J\u0119draszak, W., Majchrowicz, G., Prusinowski, F., Stabrawa, M., Rysz, J., and Franczyk, B. 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