Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 2 2 2024 07 30 78 86 Abbas Alimoradian 1. Department of Pharmacology, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Hadi Karami 2. Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran. Seied Amirhossein Latifi 3. Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran. Ali Ghazavi Department of Immunology & Microbiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Ahmad Akbari Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran. Zahra Pilevar School of Health, Arak University of Medical Sciences, Arak, Iran. Jamal Amri Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R, Iran. Students’ Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, I.R, Iran. 2025 02 10 Objectives: Diabetic nephropathy (DN) is a major complication of diabetes that requires effective treatment options. This study explores the potential benefits of saffron extract as a remedy derived from medicinal plants, focusing on its effects on key inflammatory genes—Toll-like receptor 4 (TLR-4), S100 calcium-binding protein A8 (S100A8), and High Mobility Group Box 1 (HMGB1)—as well as its role in reducing oxidative stress in the kidney tissue of rats with type 1 diabetes Methods:  The rats were randomly divided into 8 groups of 6 each. Diabetes was induced using streptozotocin (55 mg/kg.bw). Diabetic and control groups were treated with three doses of saffron extract 100, 200 and 300 mg/kg for 60 days. Biochemical kits were used to evaluate Fasting blood Glucose (FBG), urea, creatinine, albumin, lipid profile, Malondialdehyde (MDA) and total antioxidant capacity (TAC). Expression of TLR-4, S100A8, and HMGB1 genes were evaluated by real-time PCR. ANOVA and Bonferroni post-hoc tests were used for data evaluation. Results: Diabetes significantly impaired the FBG, lipid profile, creatinine, urea, and albumin levels (P<0.05). After treatment with the saffron extract, these parameters were significantly close to the normal range in all groups compared to the control group (P<0.05). Also, the saffron extract significantly decreased the expression levels of TLR-4, S100A8, and HMGB1 genes and improved oxidative stress markers (TAC and MDA) in kidney tissues when compared to the diabetic control group (P<0.05). In addition, the beneficial effects of saffron were dose-dependent. Conclusion: Based on the obtained results, the saffron extract can lead to the improvement of nephropathy by reducing the expression of TLR-4, S100A8, and HMGB1 genes as well as improving oxidative stress. Thus, it may be used as an adjuvant treatment for diabetic complications. https://abi.tums.ac.ir/index.php/abi/article/view/102 https://abi.tums.ac.ir/index.php/abi/article/download/102/59