{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:23:37Z","timestamp":1790713417381,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient\u2019s quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg\/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg\/kg b.wt), and T2DM-BBR-Vild (10 mg\/kg b.wt + Vild (5 mg\/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK\/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK\/mTOR-mediated autophagy and limiting ER stress.<\/jats:p>","DOI":"10.3390\/antiox12061220","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T01:38:26Z","timestamp":1686015506000},"page":"1220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK\/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring"],"prefix":"10.3390","volume":"12","author":[{"given":"Safaa I.","family":"Khater","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taghreed N.","family":"Almanaa","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa M. Abdel","family":"Fattah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Khamis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"},{"name":"Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona M.","family":"Seif","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-8166","authenticated-orcid":false,"given":"Naief","family":"Dahran","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah 80203, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena S.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M. M.","family":"Metwally","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6425-9247","authenticated-orcid":false,"given":"Mahmoud","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghad A.","family":"Albedair","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza I.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9951-0294","authenticated-orcid":false,"given":"Manal","family":"Alosaimi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-2675","authenticated-orcid":false,"given":"Amany Abdel-Rahman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12944-018-0676-x","article-title":"Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes","volume":"17","author":"Fan","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119674","DOI":"10.1016\/j.lfs.2021.119674","article-title":"Stabilized-chitosan selenium nanoparticles efficiently reduce renal tissue injury and regulate the expression pattern of aldose reductase in the diabetic-nephropathy rat model","volume":"279","author":"Khater","year":"2021","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145288","DOI":"10.1016\/j.gene.2020.145288","article-title":"Chitosan-stabilized selenium nanoparticles alleviate cardio-hepatic damage in type 2 diabetes mellitus model via regulation of caspase, Bax\/Bcl-2, and Fas\/FasL-pathway","volume":"768","author":"Mohamed","year":"2021","journal-title":"Gene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.12968\/bjcn.2013.18.6.267","article-title":"Interventions to promote treatment adherence in type 2 diabetes mellitus","volume":"18","author":"Asante","year":"2013","journal-title":"Br. 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