{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:28:46Z","timestamp":1790958526918,"version":"4.1.0"},"reference-count":104,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Hatieganu\u201d University of Medicine"},{"name":"Pharmacy Cluj-Napoca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE\u2019s antioxidant activity was evaluated in vitro through DPPH, H2O2, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-\u03baB, IL-1\u03b2, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride\u2013Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment.<\/jats:p>","DOI":"10.3390\/ijms26104712","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T12:22:17Z","timestamp":1747225337000},"page":"4712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multitargeted Effects of Plantago ovata Ethanol Extract in Experimental Rat Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"26","author":[{"given":"Lia-Oxana","family":"Usatiuc","sequence":"first","affiliation":[{"name":"Pathophysiology, Department 2\u2014Functional Sciences, Faculty of Medicine,\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1899-5977","authenticated-orcid":false,"given":"Raluca Maria","family":"Pop","sequence":"additional","affiliation":[{"name":"Pharmacology, Toxicology and Clinical Pharmacology, Department 2\u2014Functional Sciences, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-5239","authenticated-orcid":false,"given":"Surd","family":"Adrian","sequence":"additional","affiliation":[{"name":"Pediatric Surgery and Orthopedics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-9280","authenticated-orcid":false,"given":"Marcel","family":"P\u00e2rvu","sequence":"additional","affiliation":[{"name":"Department of Taxonomy, Faculty of Biology and Geology, \u201cBabes-Bolyai\u201d University, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u0103d\u0103lina","family":"\u021aicolea","sequence":"additional","affiliation":[{"name":"Pathophysiology, Department 2\u2014Functional Sciences, Faculty of Medicine,\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Uif\u0103lean","sequence":"additional","affiliation":[{"name":"Pathophysiology, Department 2\u2014Functional Sciences, Faculty of Medicine,\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0571-1624","authenticated-orcid":false,"given":"Dan","family":"V\u0103lean","sequence":"additional","affiliation":[{"name":"Surgery Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Ioana","family":"Gavrila\u0219","sequence":"additional","affiliation":[{"name":"Faculty of Nursing and Health Sciences, Department 2, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabo","family":"Csilla-Enik\u0151","sequence":"additional","affiliation":[{"name":"First Pediatric Clinic, Department of Mother and Child, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-1998","authenticated-orcid":false,"given":"Loredana Florina","family":"Leopold","sequence":"additional","affiliation":[{"name":"Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 3\u20135 Calea M\u0103n\u0103\u0219tur, 400372 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floricu\u021ba","family":"Ranga","sequence":"additional","affiliation":[{"name":"Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 3\u20135 Calea M\u0103n\u0103\u0219tur, 400372 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florinela Adriana","family":"C\u0103toi","sequence":"additional","affiliation":[{"name":"Pathophysiology, Department 2\u2014Functional Sciences, Faculty of Medicine,\u201cIuliu Ha\u021bieganu\u201d University of 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