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 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 diabetesmethods:  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.