{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:54:45Z","timestamp":1787586885184,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST 110-2635-B-166-001"],"award-info":[{"award-number":["MOST 110-2635-B-166-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg\/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)\/Th2\/Th17\/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-\u03b3 and tumor necrosis \u03b1 (TNF-\u03b1) by Th1 cells, and reduced interleukin (IL)-1\u03b2 and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-\u03b21 (TGF-\u03b21) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4+ subsets T cell distribution of CD4+IL-17 and CD4+ interferon gamma (IFN-\u03b3), but increased the CD4+ subsets T cell distribution of CD4+IL-4 and CD4+Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4+IL-17 and CD4+IFN\u03b3, and increased CD4+IL-4 and CD4+Foxp3 compared with the Cyp-NOD Con group (p &lt; 0.001, p &lt; 0.05, p &lt; 0.05, and p &lt; 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-\u03b3 and TNF-\u03b1 by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1\u03b2 by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing \u03b2 cells (brown), and but also enhanced the percentage of Bcl-2 (green)\/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas \u03b2 cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.<\/jats:p>","DOI":"10.3390\/ijms24129922","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"9922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antidiabetic and Immunoregulatory Activities of Extract of Phyllanthus emblica L. in NOD with Spontaneous and Cyclophosphamide-Accelerated Diabetic Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Cheng-Hsiu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Fengyuan Hospital, Ministry of Health and Welfare, Taichung City 42055, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5935-6755","authenticated-orcid":false,"given":"Yueh-Hsiung","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung City 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4264-2602","authenticated-orcid":false,"given":"Chun-Ching","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Nursing, College of Nursing, Central Taiwan University of Science and Technology, Taichung City 40601, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1056\/NEJM199411243312107","article-title":"The pathogenesis of insulin dependent diabetes mellitus","volume":"331","author":"Atkinson","year":"1994","journal-title":"N. 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