{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:23:50Z","timestamp":1773285830543,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2022-JYB-XJSJJ-017"],"award-info":[{"award-number":["2022-JYB-XJSJJ-017"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: Rhizoma Coptidis alkaloids (RCAs) have been proven highly promising in diabetes therapy. However, poor solubility, low bioavailability, and a lack of an effective delivery strategy are major hurdles to improving clinical outcomes. Herein, mPEG-PLGA nanoparticles were employed to deliver RCA orally to enhance anti-diabetic effects. Methods: The RCA-loaded nanoparticles (RCA NPs) were prepared using the emulsion solvent diffusion method. The physicochemical properties of RCA NPs were characterized by morphology, particle size, zeta potential, polydispersity index, drug loading, and drug release. Pharmacokinetic and tissue distribution were determined by UPLC-MS\/MS. The hypoglycemic effect was evaluated in a type 2 diabetes mouse model. To illustrate potential mechanisms of action, the expression of PI3K\/Akt signaling pathway-related genes and their proteins was detected by RT-PCR and Western blot, respectively. Results: The prepared RCA NPs were spherical in structure, with a particle size of approximately 145 nm and a sustained drug release profile (approximately 50% within 24 h). Compared with RCAs, RCA NP bioavailability increased approximately 2.2-fold, and the hypoglycemic, hypolipidemic, hepatoprotective, anti-inflammatory effects were significantly improved. The better outcome might be due to upregulation of expression and phosphorylation levels within the IRS1\/PI3K\/AKT\/GLUT4 signal pathway in liver tissues. Conclusions: RCA NPs hold great potential for further clinical translation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18030349","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:44:52Z","timestamp":1773229492000},"page":"349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Rhizoma Coptis Alkaloids Nanoparticle for Treating Diabetes Through Regulating PI3K\/Akt Pathways"],"prefix":"10.3390","volume":"18","author":[{"given":"Yuejiao","family":"Liu","sequence":"first","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin 300000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoqiao","family":"Su","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maofeng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin 300000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengkai","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41574-024-00979-9","article-title":"Targeting the incretin system in obesity and type 2 diabetes mellitus","volume":"20","author":"Ansari","year":"2024","journal-title":"Nat. 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