{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:51:33Z","timestamp":1787698293852,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005317","name":"Kermanshah University of Medical Sciences","doi-asserted-by":"publisher","award":["4020844"],"award-info":[{"award-number":["4020844"]}],"id":[{"id":"10.13039\/501100005317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Plant\u2010derived exosomes (PDEs) are promising nanotherapeutics for improving chronic diseases, such as diabetes mellitus.\n                      <jats:italic>Trifolium pratense<\/jats:italic>\n                      (\n                      <jats:italic>TP<\/jats:italic>\n                      ) is a flowering herb with potent antioxidant and antidiabetic properties. The present study aimed to explore the diabetic\u2010healing effects of\n                      <jats:italic>TP<\/jats:italic>\n                      \u2010derived exosomes (\n                      <jats:italic>TPDEs<\/jats:italic>\n                      ) in streptozotocin (STZ)\u2010induced diabetic rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TPDEs<\/jats:italic>\n                      were isolated using polyethylene glycol precipitation and serial centrifugation and characterised. STZ\u2010induced diabetic rats were treated with\n                      <jats:italic>TPDE<\/jats:italic>\n                      doses (0, 100, 200, and 400\u2009\u03bcg\/kg) for 28\u2009days. Biochemical factors (fasting blood sugar (FBS), insulin, C\u2010peptide, total antioxidant capacity (TAC), and nitric oxide (NO)) were evaluated in serum samples. Also, the expression of\n                      <jats:italic>PDX1, insulin, NGN3<\/jats:italic>\n                      , and\n                      <jats:italic>SIRT1<\/jats:italic>\n                      genes in pancreas tissues was assessed using real\u2010time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TPDE<\/jats:italic>\n                      treatment decreased the serum levels of FBS and NO while increasing c\u2010peptide, insulin, and TAC levels. It also significantly enhanced the expression of\n                      <jats:italic>insulin, PDX1, NGN3,<\/jats:italic>\n                      and\n                      <jats:italic>SIRT1<\/jats:italic>\n                      genes.\n                      <jats:italic>TPDEs<\/jats:italic>\n                      at doses of 100 to 200\u2009\u03bcg\/kg showed the most significant antidiabetic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TPDEs significantly improved diabetes\u2010induced alterations in serum insulin levels, antioxidant status, and pancreas\u2010related gene expression. It can be considered a novel complementary treatment for diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70103","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T01:45:21Z","timestamp":1756691121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>\n                      <i>Trifolium pratense<\/i>\n                    <\/scp>\n                    \u2010Derived Exosome Improved Serum Biochemical Parameters and Pancreatic Genes in\n                    <scp>STZ<\/scp>\n                    \u2010Induced Diabetic Rats"],"prefix":"10.1002","volume":"8","author":[{"given":"Amir Hossein","family":"Khazaei","sequence":"first","affiliation":[{"name":"Fertility and Infertility Research Center Health Technology Research Institute, Kermanshah University of Medical Sciences  Kermanshah 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