Saffron has a therapeutic effect on nephropathy by regulating the expression of TLR4, S100A8, and HMGB1 genes and reducing oxidative stress in diabetic rats

Abbas  Alimoradian; Hadi  Karami; Seied Amirhossein  Latifi; Ali  Ghazavi; Ahmad  Akbari; Zahra  Pilevar; Jamal  Amri

doi:10.18502/abi.v2i2.17934

Abbas Alimoradian Department of Pharmacology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
Hadi Karami Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Seied Amirhossein Latifi 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.

DOI: https://doi.org/10.18502/abi.v2i2.17934

Keywords: Saffron, Hydroalcoholic Extract, Oxidative stress, Gene Expression, Diabetes, rat

Abstract

Objectives: Diabetic nephropathy (DN) is a major complication of diabetes that requireseffective treatment options. This study explores the potential benefits of saffron extractas a remedy derived from medicinal plants, focusing on its effects on key inflammatorygenes—Toll-like receptor 4 (TLR-4), S100 calcium-binding protein A8 (S100A8), andHigh Mobility Group Box 1 (HMGB1)—as well as its role in reducing oxidative stressin the kidney tissue of rats with type 1 diabetes.

Methods: The rats were randomly divided into 8 groups of 6 each. Diabetes was inducedusing streptozotocin (55 mg/kg.bw). Diabetic and control groups were treated with threedoses of saffron extract (100, 200, and 300 mg/kg) for 60 days. Biochemical kits wereused 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 Bonferronipost-hoc tests were used for data evaluation.

Results: Diabetes significantly impaired the FBG, lipid profile, creatinine, urea, andalbumin levels (P<0.05). After treatment with the saffron extract, these parameterswere 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, thebeneficial effects of saffron were dose-dependent.

Conclusion: Based on the obtained results, saffron extract can lead to the improvementof nephropathy by reducing the expression of TLR-4, S100A8, and HMGB1 genes aswell as improving oxidative stress. Thus, it may be used as an adjuvant treatment fordiabetic complications.