{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:46:22Z","timestamp":1782794782535,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"University of Hail","doi-asserted-by":"publisher","award":["RG-24 082"],"award-info":[{"award-number":["RG-24 082"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In diabetes mellitus conditions, hyperglycemia leads to oxidative stress, inflammation, and \u03b2-cell dysfunction, and traditional pharmacotherapy targets only a single pathway, which gives suboptimal outcomes and drug-related problems. A novel, polyherbal ethanol extract (PHE) formulation from\n                      <jats:italic>Tinospora cordifolia, Commiphora wightii, Cinnamomum zeylanicum,<\/jats:italic>\n                      and\n                      <jats:italic>Paeonia officinalis<\/jats:italic>\n                      was evaluated for antidiabetic and organ-protective effects at different levels for multi-targeting in a streptozotocin (STZ)-induced rat model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were made diabetic using intraperitoneal administration of streptozotocin (55\u00a0mg\/kg) and randomly segregated into five groups: Normal, STZ-induced diabetic, STZ + PHE (200\u00a0mg\/kg\/day), Normal + PHE, and STZ + metformin (Met; 300\u00a0mg\/kg\/day). After 8 weeks of treatment, FBG, HbA1c, insulin, lipid profile, proinflammatory cytokines (TNF-\u03b1, IL-1\u03b2), oxidative stress biomarkers, and liver function markers were determined. Histological examination was performed on liver and pancreatic tissues with H&amp;amp;E staining, along with assessment of pancreatic insulin immunoreactivity. GC\u2013MS analysis was conducted to characterize the phytochemical constituents of PHE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PHE treatment significantly reduced FBG by 33%, HbA1c by 15%, and restored serum insulin levels (+34%) versus untreated diabetics (p &amp;lt; 0.05). Dyslipidemia was corrected, with LDL-C reduced by 30% and HDL-C increased by 46%. Hepatic ALT and AST levels were also attenuated after PHE treatment. Oxidative stress was alleviated, and TNF-\u03b1 and IL-1\u03b2 levels in the liver and pancreas were markedly suppressed. Histology showed preserved hepatocyte integrity and islet morphology, and immunohistochemistry confirmed improved \u03b2-cell integrity and enhanced insulin immunoreactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The polyherbal preparation produced impressive control over glycemia, strong antioxidant and anti-inflammatory effects, and protection of liver and pancreatic architecture. These effects translate into its potential as a phytotherapeutic candidate for safely managing diabetes and its complications, warranting further molecular and clinical research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1870583","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:25:38Z","timestamp":1782793538000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-target antidiabetic and organ-protective effects of a polyherbal ethanol extract in STZ-induced diabetic rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohd Adnan","family":"Kausar","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehkashan","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Medical Elementology and Toxicology, School of chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]},{"name":"Interdisciplinary Biotechnology Unit, Aligarh Muslim University","place":["Aligarh, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf Saleem","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Ali Abdelfattah","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab Adel Awad Abdel","family":"Razek","sequence":"additional","affiliation":[{"name":"Department of Sports Science and Physical Activity, College of Education, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhel","family":"Parvez","sequence":"additional","affiliation":[{"name":"Department of Medical Elementology and Toxicology, School of chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waseem Ahmad","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit, Aligarh Muslim University","place":["Aligarh, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/s2221-1691(13)60025-8","article-title":"Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis linn","volume":"3","author":"Ahmad","year":"2013","journal-title":"Asian Pac J. 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