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

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.